Research ArticleArticles
Open Access

Pathogenetic Dichotomy in Angioleiomyoma

IOANNIS PANAGOPOULOS, KRISTIN ANDERSEN, MARTA BRUNETTI, LUDMILA GORUNOVA, ILYÁ KOSTOLOMOV, WANJA KILDAL, HANNE REGINE HOGNESTAD, INGVILD LOBMAIER, FRANCESCA MICCI and SVERRE HEIM
Cancer Genomics & Proteomics November 2023, 20 (6) 556-566; DOI: https://doi.org/10.21873/cgp.20405

Abstract

Background/Aim: Angioleiomyoma is a benign tumor, occurs at any age, and arises most frequently in the lower extremities. Genetic information on angioleiomyomas is restricted to six reported abnormal karyotypes, losses in chromosome 22 and gains in Xq found by comparative genomic hybridization, and mutation analysis of notch receptor 2 (NOTCH2), NOTCH3, platelet-derived growth factor receptor beta (PDGFRB), and mediator complex subunit 12 (MED12) in a few tumors. Herein, we report the genetic findings in another three angioleiomyomas. Materials and Methods: The tumors were examined using G-banding and karyotyping, RNA sequencing, reverse transcription-polymerase chain reaction, Sanger sequencing, and expression analysis. Results: The first tumor carried a t(4;5)(p12;q32) translocation resulting in fusion of the cardiac mesoderm enhancer-associated non-coding RNA (CARMN in 5q32) with the TXK tyrosine kinase gene (TXK in 4p12) leading to overexpression of TXK. To our knowledge, this is the first time that a recurrent chromosome translocation and its resulting fusion gene have been described in angioleiomyomas. The second tumor carried a four-way translocation, t(X;3;4;16)(q22;p11;q11;p13) which fused the myosin heavy chain 11 gene (MYH11 in 16p13) with intergenic sequences from Xq22 that mapped a few kilobase pairs distal to the insulin receptor substrate 4 gene (IRS4), resulting in enhanced IRS4 expression. The third angioleiomyoma carried another rearrangement of chromosome band Xq22, t(X;9)(q22;q32), as the sole cytogenetic aberration, but no material was available for further molecular investigation. Conclusion: Our data, together with previously reported abnormal karyotypes in angioleiomyomas, show the presence of two recurrent genetic pathways in this tumor type: The first is characterized by presence of the translocation t(4;5)(p12;q32), which generates a CARMN::TXK chimera. The second is recurrent rearrangement of Xq22 resulting in overexpression of IRS4.

Key Words

Angioleiomyoma, also known as angiomyoma, vascular leiomyoma or dermal angioma, is a benign tumor believed to arise from the smooth muscle layer (tunica media) of subcutaneous blood vessels (1). In the World Health Organization classification of soft-tissue and bone tumors, published in 2020, angioleiomyoma is considered a distinct tumor entity which, together with glomus tumor and myopericytoma, form the group of pericytic (perivascular) tumors (2). Angioleiomyoma accounts for 5% of all benign soft tumors, may occur at any age with a peak incidence between the fourth and sixth decade of life, and may arise anywhere but most frequently in the lower extremities (3). Fewer than 50 angioleiomyomas of the knee have been reported to date (4).

Angioleiomyomas are typically firm, well-circumscribed nodules in which well-differentiated, perivascular smooth-muscle cells are arranged around numerous vascular channels (2). The tumor cells are consistently positive for smooth muscle actin (encoded by ACTA2 on 10q23.31) and the calcium-binding protein calponin 1 (encoded by the CNN1 gene on 19p13.2). They are variably positive for H-caldesmon, desmin, and vimentin but negative for pre-melanosome protein (also known as HMB45) and estrogen receptor (5, 6).

Genetic information on angioleiomyomas is limited. Abnormal karyotypes have been reported for six angioleiomyomas (Table I) (7-11). Recurrent losses from chromosome 22 and recurrent gains from Xq were found by comparative genomic hybridization (12). Rearrangement of the notch receptor 2 gene (NOTCH2) was detected in a single case (13). No mutations in exons 12 and 14 of the platelet-derived growth factor receptor beta gene (PDGFRB) were found in nine examined angioleiomyomas (14). A recent study described mutations of PDGFRB and NOTCH3 in 3/11 and 4/11 examined angioleiomyomas, respectively (15). In other studies, no mutations in exon 2 of the mediator complex subunit 12 gene (MED12) were found in 18 angioleiomyomas examined (16, 17).

View this table:
Table I.

Angioleiomyomas reported with chromosomal abnormalities.

Herein, we report the cytogenetic and molecular genetic findings in three angioleiomyomas and discuss the possible pathogenetic pathways of angioleiomyoma tumorigenesis against the background of these data as well as previously published cases.

Materials and Methods

Ethics statement. The study was approved by the regional ethics committee (Regional komité for medisinsk forskningsetikk Sør-Øst, Norge, http://helseforskning.etikkom.no). Written informed consent was obtained from the patients to publication of the case details. The ethics committee’s approval included a review of the consent procedure. All patient information has been de-identified.

Tumor description. The patients were three males aged 57, 57, and 42 years (Table II). The tumors were located in the knee, foot, and ankle, respectively. In two cases, resected tumors were used for genetic examinations whereas material from a needle biopsy was used in the third case.

View this table:
Table II.

Clinicopathological and genetic data of the study cases of angioleiomyoma.

G-Banding and karyotyping. Samples were received and analyzed cytogenetically as part of our diagnostic routine. They were disaggregated mechanically and enzymatically with collagenase II (Worthington, Freehold, NJ, USA). The resulting cells were cultured, harvested, and processed for cytogenetic examination using standard techniques (18, 19). Chromosome preparations were G-banded with Wright’s stain (Sigma-Aldrich, St Louis, MO, USA) and examined (18, 19). Metaphases were analyzed and karyograms prepared using a CytoVision computer-assisted karyotyping system (Leica Biosystems, Newcastle upon Tyne, UK). The karyotypes were described according to the International System for Human Cytogenomics Nomenclature (20).

RNA sequencing. Total RNA was extracted from frozen material of the two resected specimens (Table II) adjacent to that used for cytogenetic analysis and histological examination using miRNeasy Mini Kit (Qiagen, Hilden, Germany) and QiaCube automated purification system (Qiagen). The RNA concentration was measured with a QIAxpert microfluidic UV/VIS spectrophotometer (Qiagen). One microgram of total RNA was sent to the Genomics Core Facility (http://genomics.no/oslo/) at the Norwegian Radium Hospital, Oslo University Hospital for high-throughput paired-end RNA-sequencing. The software FusionCatcher and deFuse were used for detection of fusion transcripts (21-23). For quantification of RNA sequencing data (expression analysis), the program Kallisto was used (24). Quantification was calculated as transcripts per million (TPM) which is a measurement of the proportion of transcripts in the pool of RNA (24). Expression analysis was based on Ensembl release 95 (January 2019).

Reverse transcription-polymerase chain reaction (RT-PCR) and Sanger sequencing analyses. The primers used are described in Table III. One microgram of total RNA was reverse-transcribed using an iScript Advanced cDNA Synthesis Kit for RT-qPCR according to the manufacturer’s instructions (Bio-Rad, Hercules, CA, USA). cDNA corresponding to 20 ng total RNA was used as template in the PCR assay. The quality of the cDNA synthesis was assessed by amplification of a cDNA fragment from the ABL proto-oncogene 1, non-receptor tyrosine kinase (ABL1) gene using the primer combination ABL1-91F1/ABL1-404R1 (25). A BigDye Direct Cycle Sequencing Kit was used to perform both PCR and cycle (Sanger) sequencing according to the company’s recommendations (ThermoFisher Scientific, Waltham, MA, USA). In case 1, the primer combinations were CARMN-329F1/TXK-130R1 and CARMN-351F1/TXK-138R1; in case 2, the primer combinations were Seq3-Xq22-F1/Seq3-16p13-R1 and Seq3-Xq22-F2/Seq3-16p13-R2.

View this table:
Table III.

Designation, sequence (5′−>3′), and position in reference sequences of the forward (F) and reverse (R) primers used for direct sequencing, i.e. polymerase chain reaction amplification and Sanger sequencing analyses. The forward primers had the M13 forward primer sequence TGTAAAACGACGGCCAGT at their 5′-end. The reverse primers had the M13 reverse primer sequence CAGGAAACAGCTATGACC at their 5′-end.

Sequencing was run on an Applied Biosystems SeqStudio Genetic Analyzer system (ThermoFisher Scientific). The Basic Local Alignment Search Tool (BLAST) was used to compare the sequences obtained by Sanger sequencing with the National Center for Biotechnology Information (NCBI) reference sequences (26). In case 1, the reference sequences were NM_003328.3 for TXK tyrosine kinase (TXK) and NR_105059.1 for cardiac mesoderm enhancer-associated non-coding RNA (CARMN), which corresponds to transcript variant 1 of the long non-coding RNA.

The sequences obtained by Sanger sequencing in case 2 were compared with sequences from chromosome bands 16p13 and Xq22. On band 16p13, the sequences were NG_009299.1 which is the reference sequence for myosin heavy chain 11 (MYH11 maps on 16p13.11), and AF001548.1 which is the complete sequence of BAC clone CIT987SK-A-815A9 (on 16p13.11) and contains most of the MYH11 gene sequence. On band Xq22, the comparison was made with the sequence NC_000023.11, which is chromosome X primary assembly, BX322556.5 (complete DNA sequence of YAC clone ICI-4AC12), AL732308.7 (complete DNA sequence of BAC clone RP11-199F23), and AL928646.3 (complete DNA sequence of BAC clone CTD-2328D6).

In addition, the BLAST-like alignment tool (BLAT) and the human genome browser at UCSC were used to map the sequences obtained by Sanger sequencing, on the Human GRCh37/hg19 assembly (27, 28).

Results

G-Banding and karyotyping. G-Banding analysis of angioleiomyoma 1 detected two related clones which had the translocation t(4;5)(p12;q32) in common. The karyotype was 46,XY,t(4;5)(p12;q32)[11]/46,idem,der(10)t(3;10)(q11;p15)[2 ]/46,XY[4]. The t(4;5)(p12;q32) translocation is shown in Figure 1. In angioleiomyoma 2, G-banding analysis detected three related clones which had a four-way translocation, t(X;3;4;16)(q22;p11;q11;p13), in common. The karyotype describing the primary aberration, as well as clonal evolution, was 46,Y,t(X;3;4;16)(q22;p11;q11;p13)[7]/46,idem,t(1;5) (p36;q11)[3]/46,idem,t(6;15)(q15;q23~24),t(7;13)(q22;q34)[3]. The t(X;3;4;16)(q22;p11;q11;p13) translocation is shown in Figure 1. In angioleiomyoma 3, a single translocation between chromosome bands Xq22 and 9q32 was seen in all examined metaphases, yielding the karyotype 46,Y,t(X;9)(q22;q32)[13] (Figure 1). Thus, cases 2 and 3 had rearrangement of chromosome band Xq22 in common.

Figure 1.
Figure 1.

Cytogenetic analysis of the three angioleiomyomas. Partial karyotypes showing the derivative (der) chromosomes together with the corresponding normal chromosome homologs. For angioleiomyoma 1, der(4) and der(5) together with chromosomes 4 and 5 are shown. For angioleiomyoma 2, der(X), der(3), der(4), and der(16) together with chromosomes 3, 4, and 16 are shown. For angioleiomyoma 3, der(X), der(9), and the normal chromosome 9 are shown. Breakpoint positions are indicated by arrows.

RNA sequencing, RT-PCR, and Sanger sequencing analyses. Case 1: Analysis of the fastq files of RNA sequencing data with the FusionCatcher program detected eight CARMN::TXK chimeric transcripts (Table IV). RT-PCR together with Sanger sequencing of the PCR products confirmed the presence of a chimeric transcript in which exon 3 of CARMN from 5q32 (nt 419 in reference sequence NR_105059.1) was fused to exon 2 of TXK from 4p12 (nt 97 in Reference sequence NM_003328.3). No other fusion transcripts were examined (Figure 2).

View this table:
Table IV.

The cardiac mesoderm enhancer-associated non-coding RNA–TXK tyrosine kinase (CARMN::TXK) fusion transcripts detected in angioleiomyoma of case 1 carrying t(4;5)(p12;q32) after analysis of RNA sequencing data with the FusionCatcher program. Exons are based on the reference sequences NR_105059.1 for CARMN and NM_003328.3 for TXK.

Figure 2.
Figure 2.

Molecular genetic examination of the case 1 angioleiomyoma carrying a t(4;5)(p12;q32). A: The positions and transcription orientations (5′->3′) of the tyrosine kinase gene (TXK) and the cardiac mesoderm enhancer-associated non-coding RNA (CARMN) are shown on ideograms of chromosomes 4 and 5, respectively. B: Partial sequence chromatogram showing the junction position in exons 3 of CARMN and 2 of TXK.

Case 2: Analysis of fastq files of the RNA sequencing data with the FusionCatcher program did not detect fusion transcripts compatible with the observed t(X;3;4;16)(q22;p11;q11;p13) (data not shown). However, analysis of RNA sequencing data with the deFuse algorithm detected six transcripts in which sequences of the MYH11 gene from 16p13 were fused with sequences which mapped on chromosome band Xq22 distal but close to the insulin receptor substrate 4 (IRS4) gene (Table V and Figure 3). RT-PCR together with Sanger sequencing of the PCR products for the chimeric transcript designated in Table V as Seq 3 confirmed its presence in the tumor cells (Figure 3). No other fusion transcripts were examined.

View this table:
Table V.

Chimeric transcripts in angioleiomyoma of case 2 with t(X;3;4;16)(q22;p11;q11;p13) in which sequences of the myosin heavy chain 11 gene (MYH11) gene from 16p13 fused with sequences mapped on chromosome band Xq22 close, but distal to, the insulin receptor substrate 4 (IRS4) gene. Chimeric transcripts were detected with the deFuse algorithm.

Figure 3.
Figure 3.

Molecular genetic examination of the case 2 angioleiomyoma carrying the four-way translocation t(X;3;4;16)(q22;p11;q11;p13). A: Position of the myosin heavy chain 11 gene (MYH11) on chromosome 16. B: Alignment of the six fusion transcripts (Seq 1 to Seq 6) from Table V on chromosome 16 using the BLAT algorithm showing that part of the sequences aligned in the MYH11 locus. C: Position of the insulin receptor substrate 4 gene (IRS4) on chromosome X. D: Alignment of the six fusion transcripts (Seq 1 to Seq 6) from Table V on chromosome X showing that part of the fusion transcripts aligned on Xq22 close and distal to the IRS4 locus. E: Partial sequence chromatogram showing the junction position of the fusion sequence 3 (Seq 3 in Table V) found with the deFuse algorithm.

Expression analysis. Transcripts from the genes ACTA2, MYH11, IRS4 and TXK were quantified using the program Kallisto. The results for the transcripts with the highest expression are shown in Table VI. As expected, ACTA2 expression was high in both angioleiomyomas studied. Both also expressed MYH11 but the transcripts differed. In angioleiomyoma with t(4;5)(p12;q32), the transcript ENST00000576790.7 had the highest expression. This transcript corresponds to the transcript variant SM2A of MYH11 (NCBI reference sequence: NM_022844.3). In angioleiomyoma with t(X;3;4;16), the transcript ENST00000300036.6 had the highest expression. This transcript corresponds to the transcript variant SM1A of MYH11 (NCBI reference sequence: NM_002474.3) (Table VI). The TXK gene was significantly expressed in the tumor with t(4;5)(p12;q32) but expression was negligible in the tumor with t(X;3;4;16). In contrast, expression of IRS4 was negligible in the former but high in the latter.

View this table:
Table VI.

Expression analysis of the genes actin alpha 2, smooth muscle (ACTA2), myosin heavy chain 11 (MYH11), insulin receptor substrate 4 (IRS4), and TXK tyrosine kinase (TXK) in two angioleiomyomas using the program Kallisto: Angioleiomyoma 1 with a t(4;5)(p14;q32) and angioleiomyoma 2 with t(X;3;4;16)(q22;p11;q11;p13). Quantification was calculated as transcripts per million (TPM). Only the transcripts coding for protein are reported. Expression was based on Ensembl 96: April 2019.

Discussion

In 2010, Welborn and co-workers reported an angioleiomyoma with a t(4;5)(p12;q33) chromosomal aberration (11) (Table I). We herein present an angioleiomyoma with a t(4;5)(p12;q32) chromosomal translocation proving that a t(4;5)(p12;q32-33) translocation is recurrent in these tumors. We also show that the translocation results in a CARMN::TXK chimeric gene. To the best of our knowledge, this is the first time that a recurrent chromosomal translocation and its resulting fusion gene have been described in angioleiomyomas.

CARMN is a smooth muscle-specific long noncoding RNA located on chromosome band 5q32 and is transcribed from centromere to telomere (29). CARMN is a super enhancer-associated RNA important in differentiation and homeostasis of cardiac precursor cells (30, 31). It is evolutionarily conserved (29-31) and has many alternatively spliced isoforms. These are involved in cardiac cell specification and precursor cell lineage commitment (29-33). The noncoding CARMN physically interacts with various proteins affecting cellular biology. The interaction of CARMN with proteins SUZ12 and EZH2, which are subunits of the polycomb repressive complex 2, indicates a suppressive role during cardiac differentiation (30). Interaction of CARMN with myocardin helps preserve the contractile phenotype of vascular smooth muscle cells (29). Interaction of CARMN with the serum response factor regulates the plasticity of vascular smooth muscle cell and contributes to preventing the development of atherosclerosis (34). In the neoplastic context, fusions of CARMN with NOTCH2 were reported in glomus tumors (13, 35-38).

The TXK gene is located on chromosome band 4p12, is transcribed from centromere to telomere, and codes for a cytoplasmic protein tyrosine kinase which is a member of the TEC subfamily of non-receptor protein-tyrosine kinases (39-42). The genes encoding proteins within the TEC subfamily of non-receptor protein-tyrosine kinases include TEC in 4p12, interleukin 2-inducible T-cell kinase (ITK) in 5q31-32, BMX non-receptor tyrosine kinase (BMX) in Xp22.2, and the Bruton tyrosine kinase gene (BTK) in Xq22.1. All the members of the TEC subfamily, TXK, TEC, ITK, BMX and BTK, are selectively expressed in hematopoietic cells (39-43). TXK expression is highly restricted to the Th1/Th0 subset of T-cells (39, 40, 44). The TEX protein regulates expression of the interferon gamma gene (IFNG in 12q15) in Th1 cells (40, 44, 45).

The t(4;5)(p12;q32) chromosomal translocation in angioleiomyoma places the coding region of TXK under the control of the CARMN promoter. In smooth muscle cells, this promoter is normally highly active, causing high-level expression of the gene. Thus, the result of t(4;5)(p12;q32) is activation of TXK and deregulation of its downstream targets. Because both CARMN and TXK are transcribed from centromere to telomere, the chimeric CARMN::TXK gene is predicted to be on the der(5)t(4;5)(p12;q32) chromosome.

The tumors of cases 2 and 3 carried karyotypes in which chromosome band Xq22 was rearranged: Case 2 had a t(X;3;4;16)(q22;p11;q11;p13) whereas case 3 had a t(X;9)(q22;q32). Taking into consideration the previously reported angioleiomyoma with a t(X;10)(q22;q23.2) (9), we conclude that rearrangement of band Xq22 is a recurrent genetic event in angioleiomyoma tumorigenesis. In case 2, where material was available for molecular investigation, we showed that the complex translocation t(X;3;4;16)(q22;p11;q11;p13) resulted in fusion of highly expressed MYH11 from 16p13 with intergenic sequences from Xq22, generating six chimeric, truncated MYH11::Xq22 transcripts (Table IV). The Xq22 intergenic sequences map a few kilobase pairs distal to IRS4. Thus, the t(X;3;4;16) translocation brings the highly expressed MYH11 into the close vicinity of IRS4, causing high expression of IRS4. We hypothesize, indeed believe, that in angioleiomyomas with Xq22 rearrangements [t(X;9)(q22;q32), namely in case 3 of the present report and the tumor carrying t(X;10)(q22;q23.2) reported by Sonobe et al. (9)], the salient molecular consequence of the translocations is an increased expression of IRS4.

Rearrangements of Xq22 resulting in increased expression of IRS4 were previously reported in subungual exostosis through the translocation t(X;6)(q22;q13~14) (46, 47), and in a pediatric T-cell acute lymphoblastic leukemia (T-ALL) with t(X;7)(q22;q34) (48). In subungual exostosis, the t(X;6)(q22;q13~14) resulted in rearrangement of collagen type XII alpha 1 chain (COL12A1 from 6q13~14) whose 5′ end was moved to Xq22, close to the IRS4 locus (46, 47). The molecular consequence was overexpression of IRS4. In T-ALL, t(X;7)(q22;q34) brought IRS4 under the transcriptional control of T-cell receptor beta locus (from 7q34) regulatory elements (48). Rearrangements of Xq22/IRS4 and 14q11.2/T-cell receptor alpha-delta locus (TCRAD) were also found in a T-ALL carrying the translocation t(X;14)(q22;q11.2) (49). In a pan-cancer study, IRS4 was overexpressed in 10 different tumor types due to regulatory elements, such as enhancers being rearranged and juxtaposed near to IRS4 (50, 51). In all the above-mentioned studies, the breakpoint region in Xq22 was within the same area from which Xq22 intergenic sequences were fused to MYH11 in angioleiomyoma, generating MYH11::Xq22 chimeric transcripts.

The IRS4 gene is expressed at very low levels in many normal adult human tissues but highly so in skeletal muscle cells (52, 53) (https://www.ncbi.nlm.nih.gov/gene/8471). The IRS4 protein was found to control the phosphoinositide 3-kinase (PI3K) signaling pathway (50, 51, 54). Overexpression of IRS4 has been reported in lung cancer (55), hepatocellular carcinoma (56), and colorectal cancer (57). Because overexpression of IRS4 in human cancer results in deregulation of the PI3K pathway, IRS4 is a potential therapeutic target (50, 51, 54).

Conclusion

Despite the low number of angioleiomyomas that have been genetically analyzed, a pathogenetic dichotomy can already be discerned: a recurrent t(4;5)(p12;q32) chromosomal translocation resulting in a CARMN::TXK chimeric gene in one subset of angioleiomyomas, whereas rearrangement of chromosome band Xq22 resulting in overexpression of the IRS4 gene is seen in another. Whether other nonrandom patterns of aberration reflecting alternative pathogenetic pathways exist in this tumor type can only be established when more tumors are examined using appropriate genetic methodologies.

Footnotes

  • Conflicts of Interest

    The Authors declare that they have no potential conflicts of interest.

  • Authors’ Contributions

    IP designed and supervised the research, performed molecular genetic experiments and bioinformatics analysis, and wrote the article. KA performed molecular genetic experiments and evaluated the data. MB performed molecular genetic experiments and evaluated the data. LG performed cytogenetic analysis. IK performed bioinformatic analysis. WK performed expression analysis. HRH and IL performed the pathological examination. FM evaluated data. SH evaluated data, assisted with experimental design, and helped write the article. All Authors read and approved the final article.

  • Received June 1, 2023.
  • Revision received July 22, 2023.
  • Accepted July 24, 2023.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).

References

  1. ↵
    1. Hwang JW,
    2. Ahn JM,
    3. Kang HS,
    4. Suh JS,
    5. Kim SM,
    6. Seo JW
    : Vascular leiomyoma of an extremity: MR imaging-pathology correlation. Am J Roentgenol 171(4): 981-985, 1998. DOI: 10.2214/ajr.171.4.9762979
    OpenUrlCrossRefPubMed
  2. ↵
    1. WHO Classification of Tumours Editorial Board
    : Soft tissue and bone tumours. Fifth edition. Lyon, France, International Agency for Research on Cancer, 2020.
  3. ↵
    1. Ramesh P,
    2. Annapureddy S,
    3. Khan F,
    4. Sutaria P
    : Angioleiomyoma: a clinical, pathological and radiological review. Int J Clin Pract 58(6): 587-591, 2004. DOI: 10.1111/j.1368-5031.2004.00085.x
    OpenUrlCrossRefPubMed
  4. ↵
    1. Montemurro N,
    2. Ortenzi V,
    3. Naccarato GA,
    4. Perrini P
    : Angioleiomyoma of the knee: An uncommon cause of leg pain. A systematic review of the literature. Interdiscipl Neurosurg 22: 100877, 2020. DOI: 10.1016/j.inat.2020.100877
    OpenUrlCrossRef
  5. ↵
    1. Matsuyama A,
    2. Hisaoka M,
    3. Hashimoto H
    : Angioleiomyoma: a clinicopathologic and immunohistochemical reappraisal with special reference to the correlation with myopericytoma. Hum Pathol 38(4): 645-651, 2007. DOI: 10.1016/j.humpath.2006.10.012
    OpenUrlCrossRefPubMed
  6. ↵
    1. Mocellin S
    1. Mocellin S
    : Angioleiomyoma. In: Soft Tissue Tumors: A Practical and Comprehensive Guide to Sarcomas and Benign Neoplasms. Mocellin S (ed.). Cham, Switzerland, Springer International Publishing, pp. 85-86, 2021.
  7. ↵
    1. Heim S,
    2. Mandahl N,
    3. Kristoffersson U,
    4. Mitelman F,
    5. Rööser B,
    6. Rydholm A,
    7. Willén H
    : Structural chromosome aberrations in a case of angioleiomyoma. Cancer Genet Cytogenet 20(3-4): 325-330, 1986. DOI: 10.1016/0165-4608(86)90091-9
    OpenUrlCrossRefPubMed
    1. Nilbert M,
    2. Mandahl N,
    3. Heim S,
    4. Rydholm A,
    5. Willén H,
    6. Mitelman F
    : Cytogenetic abnormalities in an angioleiomyoma. Cancer Genet Cytogenet 37(1): 61-64, 1989. DOI: 10.1016/0165-4608(89)90075-7
    OpenUrlCrossRefPubMed
  9. ↵
    1. Sonobe H,
    2. Ohtsuki Y,
    3. Mizobuchi H,
    4. Toda M,
    5. Shimizu K
    : An angiomyoma with t(X;10)(q22;q23.2). Cancer Genet Cytogenet 90(1): 54-56, 1996. DOI: 10.1016/0165-4608(96)00070-2
    OpenUrlCrossRefPubMed
    1. Hennig Y,
    2. Caselitz J,
    3. Stern C,
    4. Bartnitzke S,
    5. Bullerdiek J
    : Karyotype evolution in a case of uterine angioleiomyoma. Cancer Genet Cytogenet 108(1): 79-80, 1999. DOI: 10.1016/s0165-4608(98)00123-x
    OpenUrlCrossRefPubMed
  11. ↵
    1. Welborn J,
    2. Fenner S,
    3. Parks R
    : Angioleiomyoma: a benign tumor with karyotypic aberrations. Cancer Genet Cytogenet 199(2): 147-148, 2010. DOI: 10.1016/j.cancergencyto.2010.01.022
    OpenUrlCrossRefPubMed
  12. ↵
    1. Nishio J,
    2. Iwasaki H,
    3. Ohjimi Y,
    4. Ishiguro M,
    5. Kobayashi K,
    6. Nabeshima K,
    7. Naito M,
    8. Kikuchi M
    : Chromosomal imbalances in angioleiomyomas by comparative genomic hybridization. Int J Mol Med 13(1): 13-16, 2004.
    OpenUrlPubMed
  13. ↵
    1. Mosquera JM,
    2. Sboner A,
    3. Zhang L,
    4. Chen CL,
    5. Sung YS,
    6. Chen HW,
    7. Agaram NP,
    8. Briskin D,
    9. Basha BM,
    10. Singer S,
    11. Rubin MA,
    12. Tuschl T,
    13. Antonescu CR
    : Novel MIR143-NOTCH fusions in benign and malignant glomus tumors. Genes Chromosomes Cancer 52(11): 1075-1087, 2013. DOI: 10.1002/gcc.22102
    OpenUrlCrossRefPubMed
  14. ↵
    1. Agaimy A,
    2. Bieg M,
    3. Michal M,
    4. Geddert H,
    5. Märkl B,
    6. Seitz J,
    7. Moskalev EA,
    8. Schlesner M,
    9. Metzler M,
    10. Hartmann A,
    11. Wiemann S,
    12. Michal M,
    13. Mentzel T,
    14. Haller F
    : Recurrent somatic PDGFRB mutations in sporadic infantile/solitary adult myofibromas but not in angioleiomyomas and myopericytomas. Am J Surg Pathol 41(2): 195-203, 2017. DOI: 10.1097/pas.0000000000000752
    OpenUrlCrossRef
  15. ↵
    1. Iwamura R,
    2. Komatsu K,
    3. Kusano M,
    4. Kubo C,
    5. Inaba Y,
    6. Shiba E,
    7. Nawata A,
    8. Tajiri R,
    9. Matsuyama A,
    10. Matoba H,
    11. Koga K,
    12. Takeda M,
    13. Itami H,
    14. Hisaoka M
    : PDGFRB and NOTCH3 mutations are detectable in a wider range of pericytic tumors, including myopericytomas, angioleiomyomas, glomus tumors, and their combined tumors. Modern Pathology 36(3): 100070, 2023. DOI: 10.1016/j.modpat.2022.100070
    OpenUrlCrossRef
  16. ↵
    1. de Graaff MA,
    2. Cleton-Jansen A,
    3. Szuhai K,
    4. Bovée JV
    : Mediator complex subunit 12 exon 2 mutation analysis in different subtypes of smooth muscle tumors confirms genetic heterogeneity. Human Pathology 44(8): 1597-1604, 2013. DOI: 10.1016/j.humpath.2013.01.006
    OpenUrlCrossRefPubMed
  17. ↵
    1. Matsubara A,
    2. Sekine S,
    3. Yoshida M,
    4. Yoshida A,
    5. Taniguchi H,
    6. Kushima R,
    7. Tsuda H,
    8. Kanai Y
    : Prevalence of MED12 mutations in uterine and extrauterine smooth muscle tumours. Histopathology 62(4): 657-661, 2013. DOI: 10.1111/his.12039
    OpenUrlCrossRefPubMed
  18. ↵
    1. Polito P,
    2. Dal Cin P,
    3. Debiec-Rychter M,
    4. Hagemeijer A
    : Human solid tumors: Cytogenetic techniques. Methods Mol Biol 220: 135-150, 2003. DOI: 10.1385/1-59259-363-1:135
    OpenUrlCrossRefPubMed
  19. ↵
    1. Lukeis R,
    2. Suter M
    : Cytogenetics of solid tumours. Methods Mol Biol 730: 173-187, 2011. DOI: 10.1007/978-1-61779-074-4_13
    OpenUrlCrossRefPubMed
  20. ↵
    1. McGowan-Jordan J,
    2. Hastings RJ,
    3. Moore S
    : ISCN2020: an international system for human cytogenomic nomenclature. Basel, Switzerland, Karger, pp. 164, 2020.
  21. ↵
    1. Kangaspeska S,
    2. Hultsch S,
    3. Edgren H,
    4. Nicorici D,
    5. Murumägi A,
    6. Kallioniemi O
    : Reanalysis of RNA-sequencing data reveals several additional fusion genes with multiple isoforms. PLoS One 7(10): e48745, 2012. DOI: 10.1371/journal.pone.0048745
    OpenUrlCrossRefPubMed
    1. Nicorici D,
    2. Satalan H,
    3. Edgren H,
    4. Kangaspeska S,
    5. Murumagi A,
    6. Kallioniemi O,
    7. Virtanen S,
    8. Kikku O
    : FusionCatcher - a tool for finding somatic fusion genes in paired-end RNA-sequencing data. bioRxiv, 2014. DOI: 10.1101/011650
    OpenUrlAbstract/FREE Full Text
  23. ↵
    1. McPherson A,
    2. Hormozdiari F,
    3. Zayed A,
    4. Giuliany R,
    5. Ha G,
    6. Sun MG,
    7. Griffith M,
    8. Heravi Moussavi A,
    9. Senz J,
    10. Melnyk N,
    11. Pacheco M,
    12. Marra MA,
    13. Hirst M,
    14. Nielsen TO,
    15. Sahinalp SC,
    16. Huntsman D,
    17. Shah SP
    : deFuse: an algorithm for gene fusion discovery in tumor RNA-Seq data. PLoS Comput Biol 7(5): e1001138, 2011. DOI: 10.1371/journal.pcbi.1001138
    OpenUrlCrossRefPubMed
  24. ↵
    1. Bray NL,
    2. Pimentel H,
    3. Melsted P,
    4. Pachter L
    : Near-optimal probabilistic RNA-seq quantification. Nat Biotechnol 34(5): 525-527, 2016. DOI: 10.1038/nbt.3519
    OpenUrlCrossRefPubMed
  25. ↵
    1. Torkildsen S,
    2. Brunetti M,
    3. Gorunova L,
    4. Spetalen S,
    5. Beiske K,
    6. Heim S,
    7. Panagopoulos I
    : Rearrangement of the chromatin organizer special AT-rich binding protein 1 gene, SATB1, resulting from a t(3;5)(p24;q14) chromosomal translocation in acute myeloid leukemia. Anticancer Res 37(2): 693-698, 2017. DOI: 10.21873/anticanres.11365
    OpenUrlAbstract/FREE Full Text
  26. ↵
    1. Altschul SF,
    2. Gish W,
    3. Miller W,
    4. Myers EW,
    5. Lipman DJ
    : Basic local alignment search tool. J Mol Biol 215(3): 403-410, 1990. DOI: 10.1016/S0022-2836(05)80360-2
    OpenUrlCrossRefPubMed
  27. ↵
    1. Kent WJ
    : BLAT—the BLAST-like alignment tool. Genome Res 12(4): 656-664, 2002. DOI: 10.1101/gr.229202
    OpenUrlAbstract/FREE Full Text
  28. ↵
    1. Kent WJ,
    2. Sugnet CW,
    3. Furey TS,
    4. Roskin KM,
    5. Pringle TH,
    6. Zahler AM,
    7. Haussler D
    : The human genome browser at UCSC. Genome Res 12(6): 996-1006, 2002. DOI: 10.1101/gr.229102
    OpenUrlAbstract/FREE Full Text
  29. ↵
    1. Dong K,
    2. Shen J,
    3. He X,
    4. Hu G,
    5. Wang L,
    6. Osman I,
    7. Bunting KM,
    8. Dixon-Melvin R,
    9. Zheng Z,
    10. Xin H,
    11. Xiang M,
    12. Vazdarjanova A,
    13. Fulton DJR,
    14. Zhou J
    : CARMN is an evolutionarily conserved smooth muscle cell-specific LncRNA that maintains contractile phenotype by binding myocardin. Circulation 144(23): 1856-1875, 2021. DOI: 10.1161/CIRCULATIONAHA.121.055949
    OpenUrlCrossRef
  30. ↵
    1. Ounzain S,
    2. Micheletti R,
    3. Arnan C,
    4. Plaisance I,
    5. Cecchi D,
    6. Schroen B,
    7. Reverter F,
    8. Alexanian M,
    9. Gonzales C,
    10. Ng SY,
    11. Bussotti G,
    12. Pezzuto I,
    13. Notredame C,
    14. Heymans S,
    15. Guigó R,
    16. Johnson R,
    17. Pedrazzini T
    : CARMEN, a human super enhancer-associated long noncoding RNA controlling cardiac specification, differentiation and homeostasis. J Mol Cell Cardiol 89: 98-112, 2015. DOI: 10.1016/j.yjmcc.2015.09.016
    OpenUrlCrossRefPubMed
  31. ↵
    1. Ounzain S,
    2. Pedrazzini T
    : Super-enhancer lncs to cardiovascular development and disease. Biochim Biophys Acta 1863(7): 1953-1960, 2016. DOI: 10.1016/j.bbamcr.2015.11.026
    OpenUrlCrossRef
    1. Plaisance I,
    2. Perruchoud S,
    3. Fernandez-Tenorio M,
    4. Gonzales C,
    5. Ounzain S,
    6. Ruchat P,
    7. Nemir M,
    8. Niggli E,
    9. Pedrazzini T
    : Cardiomyocyte lineage specification in adult human cardiac precursor cells via modulation of enhancer-associated long noncoding RNA expression. JACC Basic Transl Sci 1(6): 472-493, 2016. DOI: 10.1016/j.jacbts.2016.06.008
    OpenUrlAbstract/FREE Full Text
  33. ↵
    1. Plaisance I,
    2. Chouvardas P,
    3. Sun Y,
    4. Nemir M,
    5. Aghagolzadeh P,
    6. Aminfar F,
    7. Shen S,
    8. Shim WJ,
    9. Rochais F,
    10. Johnson R,
    11. Palpant N,
    12. Pedrazzini T
    : A transposable element into the human long noncoding RNA CARMEN is a switch for cardiac precursor cell specification. Cardiovasc Res 119(6): 1361-1376, 2023. DOI: 10.1093/cvr/cvac191
    OpenUrlCrossRef
  34. ↵
    1. Ni H,
    2. Haemmig S,
    3. Deng Y,
    4. Chen J,
    5. Simion V,
    6. Yang D,
    7. Sukhova G,
    8. Shvartz E,
    9. Wara AKMK,
    10. Cheng HS,
    11. Pérez-Cremades D,
    12. Assa C,
    13. Sausen G,
    14. Zhuang R,
    15. Dai Q,
    16. Feinberg MW
    : A smooth muscle cell-enriched long noncoding RNA regulates cell plasticity and atherosclerosis by interacting with serum response factor. Arterioscler Thromb Vasc Biol 41(9): 2399-2416, 2021. DOI: 10.1161/ATVBAHA.120.315911
    OpenUrlCrossRef
  35. ↵
    1. Girard N,
    2. Marin C,
    3. Hélias-Rodzewicz Z,
    4. Villa C,
    5. Julié C,
    6. de Lajarte-Thirouard AS,
    7. de Beauce SM,
    8. Lagorce-Pages C,
    9. Renaud F,
    10. Cazals-Hatem D,
    11. Guedj N,
    12. Cros J,
    13. Raffin-Sanson ML,
    14. Selves J,
    15. Terris B,
    16. Fléjou JF,
    17. Garchon HJ,
    18. Coindre JM,
    19. Emile JF
    : CARMN-NOTCH2 fusion transcript drives high NOTCH2 expression in glomus tumors of the upper digestive tract. Genes Chromosomes Cancer 60(11): 723-732, 2021. DOI: 10.1002/gcc.22981
    OpenUrlCrossRef
    1. Larsen N,
    2. Pavlidakey P,
    3. Harada S,
    4. Prieto-Granada CN
    : Cutaneous malignant glomus tumor with an MIR143(CARMN)::NOTCH2 fusion. J Cutan Pathol 50(2): 101-103, 2022. DOI: 10.1111/cup.14351
    OpenUrlCrossRef
    1. Miao R,
    2. Bui MM,
    3. Walko C,
    4. Mullinax JE,
    5. Brohl AS
    : A malignant glomus tumor of the liver harboring MIR143-NOTCH2 rearrangement: from diagnosis to management. Cureus 14(10): e30718, 2022. DOI: 10.7759/cureus.30718
    OpenUrlCrossRef
  38. ↵
    1. Papke DJ,
    2. Sholl LM,
    3. Doyle LA,
    4. Fletcher CD,
    5. Hornick JL
    : Gastroesophageal glomus tumors. Am J Surg Pathol 46(10): 1436-1446, 2022. DOI: 10.1097/pas.0000000000001925
    OpenUrlCrossRef
  39. ↵
    1. Haire RN,
    2. Ohta Y,
    3. Lewis JE,
    4. Fu SM,
    5. Kroisel P,
    6. Litman GW
    : TXK, a novel human tyrosine kinase expressed in T cells shares sequence identity with Tec family kinases and maps to 4p12. Hum Mol Genet 3(6): 897-901, 1994. DOI: 10.1093/hmg/3.6.897
    OpenUrlCrossRefPubMed
  40. ↵
    1. Kashiwakura J,
    2. Suzuki N,
    3. Nagafuchi H,
    4. Takeno M,
    5. Takeba Y,
    6. Shimoyama Y,
    7. Sakane T
    : Txk, a nonreceptor tyrosine kinase of the Tec family, is expressed in T helper type 1 cells and regulates interferon gamma production in human T lymphocytes. J Exp Med 190(8): 1147-1154, 1999. DOI: 10.1084/jem.190.8.1147
    OpenUrlAbstract/FREE Full Text
    1. Smith CE,
    2. Islam TC,
    3. Mattsson PT,
    4. Mohamed AJ,
    5. Nore BF,
    6. Vihinen M
    : The Tec family of cytoplasmic tyrosine kinases: mammalian Btk, Bmx, Itk, Tec, Txk and homologs in other species. Bioessays 23(5): 436-446, 2001. DOI: 10.1002/bies.1062
    OpenUrlCrossRefPubMed
  42. ↵
    1. Yin Z,
    2. Zou Y,
    3. Wang D,
    4. Huang X,
    5. Xiong S,
    6. Cao L,
    7. Zhang Y,
    8. Sun Y,
    9. Zhang N
    : Regulation of the Tec family of non-receptor tyrosine kinases in cardiovascular disease. Cell Death Discov 8(1): 119, 2022. DOI: 10.1038/s41420-022-00927-4
    OpenUrlCrossRef
  43. ↵
    1. Hu Q,
    2. Davidson D,
    3. Schwartzberg PL,
    4. Macchiarini F,
    5. Lenardo MJ,
    6. Bluestone JA,
    7. Matis LA
    : Identification of Rlk, a novel protein tyrosine kinase with predominant expression in the T cell lineage. J Biol Chem 270(4): 1928-1934, 1995. DOI: 10.1074/jbc.270.4.1928
    OpenUrlAbstract/FREE Full Text
  44. ↵
    1. Takeba Y,
    2. Nagafuchi H,
    3. Takeno M,
    4. Kashiwakura J,
    5. Suzuki N
    : Txk, a member of nonreceptor tyrosine kinase of tec family, acts as a Th1 cell-specific transcription factor and regulates IFN-γ gene transcription. J Immunol 168(5): 2365-2370, 2002. DOI: 10.4049/jimmunol.168.5.2365
    OpenUrlAbstract/FREE Full Text
  45. ↵
    1. Maruyama T,
    2. Nara K,
    3. Yoshikawa H,
    4. Suzuki N
    : Txk, a member of the non-receptor tyrosine kinase of the Tec family, forms a complex with poly(ADP-ribose) polymerase 1 and elongation factor 1alpha and regulates interferon-gamma gene transcription in Th1 cells. Clin Exp Immunol 147(1): 164-175, 2007. DOI: 10.1111/j.1365-2249.2006.03249.x
    OpenUrlCrossRefPubMed
  46. ↵
    1. Storlazzi CT,
    2. Wozniak A,
    3. Panagopoulos I,
    4. Sciot R,
    5. Mandahl N,
    6. Mertens F,
    7. Debiec-Rychter M
    : Rearrangement of the COL12A1 and COL4A5 genes in subungual exostosis: molecular cytogenetic delineation of the tumor-specific translocationt(X;6) (q13-14;q22). Int J Cancer 118(8): 1972-1976, 2006. DOI: 10.1002/ijc.21586
    OpenUrlCrossRefPubMed
  47. ↵
    1. Mertens F,
    2. Möller E,
    3. Mandahl N,
    4. Picci P,
    5. Perez-Atayde AR,
    6. Samson I,
    7. Sciot R,
    8. Debiec-Rychter M
    : The t(X;6) in subungual exostosis results in transcriptional deregulation of the gene for insulin receptor substrate 4. Int J Cancer 128(2): 487-491, 2011. DOI: 10.1002/ijc.25353
    OpenUrlCrossRefPubMed
  48. ↵
    1. Karrman K,
    2. Kjeldsen E,
    3. Lassen C,
    4. Isaksson M,
    5. Davidsson J,
    6. Andersson A,
    7. Hasle H,
    8. Fioretos T,
    9. Johansson B
    : The t(X;7)(q22;q34) in paediatric T-cell acute lymphoblastic leukaemia results in overexpression of the insulin receptor substrate 4 gene through illegitimate recombination with the T-cell receptor beta locus. Br J Haematol 144(4): 546-551, 2009. DOI: 10.1111/j.1365-2141.2008.07453.x
    OpenUrlCrossRefPubMed
  49. ↵
    1. Kang DH,
    2. Kim SH,
    3. Jun JW,
    4. Lee YW,
    5. Shin HB,
    6. Ahn JY,
    7. Hong DS,
    8. Lee YK,
    9. Jeon BR
    : Simultaneous translocation of both TCR Loci (14q11) with rare partner loci (Xq22 and 12p13) in a case of T-lymphoblastic leukemia. Ann Lab Med 32(3): 220-224, 2012. DOI: 10.3343/alm.2012.32.3.220
    OpenUrlCrossRefPubMed
  50. ↵
    1. Ikink GJ,
    2. Hilkens J
    : Insulin receptor substrate 4 (IRS4) is a constitutive active oncogenic driver collaborating with HER2 and causing therapeutic resistance. Mol Cell Oncol 4(2): e1279722, 2017. DOI: 10.1080/23723556.2017.1279722
    OpenUrlCrossRef
  51. ↵
    1. Weischenfeldt J,
    2. Dubash T,
    3. Drainas AP,
    4. Mardin BR,
    5. Chen Y,
    6. Stütz AM,
    7. Waszak SM,
    8. Bosco G,
    9. Halvorsen AR,
    10. Raeder B,
    11. Efthymiopoulos T,
    12. Erkek S,
    13. Siegl C,
    14. Brenner H,
    15. Brustugun OT,
    16. Dieter SM,
    17. Northcott PA,
    18. Petersen I,
    19. Pfister SM,
    20. Schneider M,
    21. Solberg SK,
    22. Thunissen E,
    23. Weichert W,
    24. Zichner T,
    25. Thomas R,
    26. Peifer M,
    27. Helland A,
    28. Ball CR,
    29. Jechlinger M,
    30. Sotillo R,
    31. Glimm H,
    32. Korbel JO
    : Pan-cancer analysis of somatic copy-number alterations implicates IRS4 and IGF2 in enhancer hijacking. Nat Genet 49(1): 65-74, 2017. DOI: 10.1038/ng.3722
    OpenUrlCrossRefPubMed
  52. ↵
    1. Sesti G,
    2. Federici M,
    3. Hribal ML,
    4. Lauro D,
    5. Sbraccia P,
    6. Lauro R
    : Defects of the insulin receptor substrate (IRS) system in human metabolic disorders. FASEB J 15(12): 2099-2111, 2001. DOI: 10.1096/fj.01-0009rev
    OpenUrlCrossRefPubMed
  53. ↵
    1. Schreyer S,
    2. Ledwig D,
    3. Rakatzi I,
    4. Klöting I,
    5. Eckel J
    : Insulin receptor substrate-4 is expressed in muscle tissue without acting as a substrate for the insulin receptor. Endocrinology 144(4): 1211-1218, 2003. DOI: 10.1210/en.2002-220723
    OpenUrlCrossRefPubMed
  54. ↵
    1. Hoxhaj G,
    2. Dissanayake K,
    3. MacKintosh C
    : Effect of IRS4 levels on PI 3-kinase signalling. PLoS One 8(9): e73327, 2013. DOI: 10.1371/journal.pone.0073327
    OpenUrlCrossRefPubMed
  55. ↵
    1. Hao P,
    2. Huang Y,
    3. Peng J,
    4. Yu J,
    5. Guo X,
    6. Bao F,
    7. Dian Z,
    8. An S,
    9. Xu T
    : IRS4 promotes the progression of non-small cell lung cancer and confers resistance to EGFR-TKI through the activation of PI3K/Akt and Ras-MAPK pathways. Exp Cell Res 403(2): 112615, 2021. DOI: 10.1016/j.yexcr.2021.112615
    OpenUrlCrossRef
  56. ↵
    1. Guijarro LG,
    2. Sanmartin-Salinas P,
    3. Pérez-Cuevas E,
    4. Toledo-Lobo MV,
    5. Monserrat J,
    6. Zoullas S,
    7. Sáez MA,
    8. Álvarez-Mon MA,
    9. Bujan J,
    10. Noguerales-Fraguas F,
    11. Arilla-Ferreiro E,
    12. Álvarez-Mon M,
    13. Ortega MA
    : Possible role of IRS-4 in the origin of multifocal hepatocellular carcinoma. Cancers (Basel) 13(11): 2560, 2021. DOI: 10.3390/cancers13112560
    OpenUrlCrossRef
  57. ↵
    1. Sanmartín-Salinas P,
    2. Toledo-Lobo MV,
    3. Noguerales-Fraguas F,
    4. Fernández-Contreras M,
    5. Guijarro LG
    : Overexpression of insulin receptor substrate-4 is correlated with clinical staging in colorectal cancer patients. J Mol Histol 49(1): 39-49, 2018. DOI: 10.1007/s10735-017-9745-0
    OpenUrlCrossRef
Back to top

In this issue

Print
Download PDF
Article Alerts
Email Article
Citation Tools
Reprints and Permissions
Pathogenetic Dichotomy in Angioleiomyoma
IOANNIS PANAGOPOULOS, KRISTIN ANDERSEN, MARTA BRUNETTI, LUDMILA GORUNOVA, ILYÁ KOSTOLOMOV, WANJA KILDAL, HANNE REGINE HOGNESTAD, INGVILD LOBMAIER, FRANCESCA MICCI, SVERRE HEIM
Cancer Genomics & Proteomics Nov 2023, 20 (6) 556-566; DOI: 10.21873/cgp.20405
Reddit logo Twitter logo Facebook logo Mendeley logo

Jump to section

Keywords