Genes, Chromosomes & Cancer最新文献

{"title":"Genomic profiling of pleomorphic rhabdomyosarcoma reveals a genomic signature distinct from that of embryonal rhabdomyosarcoma","authors":"Carla Saoud,&nbsp;Josephine K. Dermawan,&nbsp;Aarti E. Sharma,&nbsp;William Tap,&nbsp;Leonard H. Wexler,&nbsp;Cristina R. Antonescu","doi":"10.1002/gcc.23238","DOIUrl":"https://doi.org/10.1002/gcc.23238","url":null,"abstract":"<p>Pleomorphic rhabdomyosarcoma (PRMS) is a rare and highly aggressive sarcoma, occurring mostly in the deep soft tissues of middle-aged adults and showing a variable degree of skeletal muscle differentiation. The diagnosis is challenging as pathologic features overlap with embryonal rhabdomyosarcoma (ERMS), malignant Triton tumor, and other pleomorphic sarcomas. As recurrent genetic alterations underlying PRMS have not been described to date, ancillary molecular diagnostic testing is not useful in subclassification. Herein, we perform genomic profiling of a well-characterized cohort of 14 PRMS, compared to a control group of 23 ERMS and other pleomorphic sarcomas (undifferentiated pleomorphic sarcoma and pleomorphic liposarcoma) using clinically validated DNA-targeted Next generation sequencing (NGS) panels (MSK-IMPACT). The PRMS cohort included eight males and six females, with a median age of 53 years (range 31–76 years). Despite similar tumor mutation burdens, the genomic landscape of PRMS, with a high frequency of <i>TP53</i> (79%) and <i>RB1</i> (43%) alterations, stood in stark contrast to ERMS, with 4% and 0%, respectively. <i>CDKN2A</i> deletions were more common in PRMS (43%), compared to ERMS (13%). In contrast, ERMS harbored somatic driver mutations in the RAS pathway and loss of function mutations in <i>BCOR</i>, which were absent in PRMS. Copy number variations in PRMS showed multiple chromosomal arm-level changes, most commonly gains of chr17p and chr22q and loss of chr6q. Notably, gain of chr8, commonly seen in ERMS (61%) was conspicuously absent in PRMS. The genomic profiles of other pleomorphic sarcomas were overall analogous to PRMS, showing shared alterations in <i>TP53</i>, <i>RB1</i>, and <i>CDKN2A</i>. Overall survival and progression-free survival of PRMS were significantly worse (<i>p</i> &lt; 0.0005) than that of ERMS. Our findings revealed that the molecular landscape of PRMS aligns with other adult pleomorphic sarcomas and is distinct from that of ERMS. Thus, NGS assays may be applied in select challenging cases toward a refined classification. Finally, our data corroborate the inclusion of PRMS in the therapeutic bracket of pleomorphic sarcomas, given that their clinical outcomes are comparable.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 5","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140895196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delineating genotype and parent-of-origin effect on the phenotype in MSH6-associated Lynch syndrome","authors":"Anne-Sophie van der Werf-'t Lam,&nbsp;Mar Rodriguez-Girondo,&nbsp;Mandy Villasmil,&nbsp;Carli M. Tops,&nbsp;Liselotte van Hest,&nbsp;Hans J. P. Gille,&nbsp;Floor A. M. Duijkers,&nbsp;Anja Wagner,&nbsp;Ellis Eikenboom,&nbsp;Tom G. W. Letteboer,&nbsp;Mirjam M. de Jong,&nbsp;Sanne W. Bajwa-ten Broeke,&nbsp;Fonnet Bleeker,&nbsp;Encarna B. Gomez Garcia,&nbsp;Mev Dominguez-Valentin,&nbsp;Pal Møller,&nbsp;Manon Suerink,&nbsp;Maartje Nielsen","doi":"10.1002/gcc.23237","DOIUrl":"https://doi.org/10.1002/gcc.23237","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>This study investigates the potential influence of genotype and parent-of-origin effects (POE) on the clinical manifestations of Lynch syndrome (LS) within families carrying (likely) disease-causing <i>MSH6</i> germline variants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients and Methods</h3>\u0000 \u0000 <p>A cohort of 1615 <i>MSH6</i> variant carriers (310 LS families) was analyzed. Participants were categorized based on RNA expression and parental inheritance of the variant. Hazard ratios (HRs) were calculated using weighted Cox regression, considering external information to address ascertainment bias. The findings were cross-validated using the Prospective Lynch Syndrome Database (PLSD) for endometrial cancer (EC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No significant association was observed between genotype and colorectal cancer (CRC) risk (HR = 1.06, 95% confidence interval [CI]: 0.77–1.46). Patients lacking expected RNA expression exhibited a reduced risk of EC (Reference Cohort 1: HR = 0.68, 95% CI: 0.43–1.03; Reference Cohort 2: HR = 0.63, 95% CI: 0.46–0.87). However, these results could not be confirmed in the PLSD. Moreover, no association was found between POE and CRC risk (HR = 0.78, 95% CI: 0.52–1.17) or EC risk (Reference Cohort 1: HR = 0.93, 95% CI: 0.65–1.33; Reference Cohort 2: HR = 0.8, 95% CI: 0.64–1.19).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion and Conclusion</h3>\u0000 \u0000 <p>No evidence of POE was detected in <i>MSH6</i> families. While RNA expression may be linked to varying risks of EC, further investigation is required to explore this observation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 5","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23237","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140895195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathologic and molecular correlates to neoadjuvant chemotherapy-induced pathologic response in breast angiosarcoma","authors":"Hsin-Yi Chang,&nbsp;Josephine K. Dermawan,&nbsp;Maria Gabriela Kuba,&nbsp;Aimee M. Crago,&nbsp;Samuel Singer,&nbsp;William Tap,&nbsp;Ping Chi,&nbsp;Sandra D'Angelo,&nbsp;Evan Rosenbaum,&nbsp;Cristina R. Antonescu","doi":"10.1002/gcc.23240","DOIUrl":"https://doi.org/10.1002/gcc.23240","url":null,"abstract":"<p>Both primary and secondary breast angiosarcoma (AS) are characterized by multifocal presentation and aggressive behavior. Despite multimodality therapy, local and distant relapse rates remain high. Therefore, neoadjuvant chemotherapy (NACT) is employed to improve the R0 resection rates and survival, but its benefits remain controversial. Herein, we investigate pathologic and molecular correlates to NACT-induced histologic response in a group of 29 breast AS, 4 primary and 25 radiation-associated (RA). The two NACT regimens applied were anthracycline- and non-anthracycline-based. The pathologic response grade was defined as: I: ≤ 50%, II: 51%–90%, III: 91%–99%, and IV: 100%. An additional 45 primary AS and 102 RA-AS treated by surgery alone were included for survival comparison. The genomic landscape was analyzed in a subset of cases and compared to a cohort of AS without NACT on a paired tumor-normal targeted DNA NGS platform. All patients were females, with a median age of 31 years in primary AS and 68 years in RA-AS. All surgical margins were negative in NACT group. The NACT response was evenly divided between poor (Grades I–II; <i>n</i> = 15) and good responders (Grades III–IV; <i>n</i> = 14). Mitotic count &gt;10/mm² was the only factor inversely associated with pathologic response. By targeted NGS, all 10 post-NACT RA-AS demonstrated <i>MYC</i> amplification, while both primary AS harbored <i>KDR</i> mutations. TMB or other genomic alterations did not correlate with pathologic response. All four patients with Grade IV response remained free of disease. The good responders had a significantly better disease-specific survival (<i>p</i> = 0.04). There was no survival difference with NACT status or the NACT regimens applied. However, NACT patients with <i>MYC</i>-amplified tumors showed better disease-free survival (<i>p</i> = 0.04) compared to <i>MYC</i>-amplified patients without NACT. The overall survival of NACT group correlated with size &gt;10 cm (<i>p</i> = 0.02), pathologic response (<i>p</i> = 0.04), and multifocality (<i>p</i> = 0.01) by univariate, while only size &gt;10 cm (<i>p</i> = 0.03) remained significant by multivariate analysis.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 5","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140895197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal trends and regional variability in BRAF and KRAS genetic testing in Denmark (2010–2022): Implications for precision medicine","authors":"Matilde Grupe Frost,&nbsp;Kristoffer Jarlov Jensen,&nbsp;Espen Jimenez-Solem,&nbsp;Camilla Qvortrup,&nbsp;Tine Plato Kuhlmann,&nbsp;Jon Lykkegaard Andersen,&nbsp;Estrid Høgdall,&nbsp;Tonny Studsgaard Petersen","doi":"10.1002/gcc.23236","DOIUrl":"https://doi.org/10.1002/gcc.23236","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aims to evaluate the developments in the testing of Kirsten Rat Sarcoma viral oncogene homolog (KRAS) and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations across different cancer types and regions in Denmark from 2010 to 2022.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Study design and setting</h3>\u0000 \u0000 <p>Using comprehensive data from the Danish health registries, we linked molecular test results from the Danish Pathology Registry with cancer diagnoses from the Danish National Patient Registry between 2010 and 2022. We assessed the frequency and distribution of KRAS and BRAF mutations across all cancer types, years of testing, and the five Danish regions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study included records of KRAS testing for 30 671 patients and BRAF testing for 30 860 patients. Most KRAS testing was performed in colorectal (78%) and lung cancer (18%), and BRAF testing in malignant melanoma (13%), colorectal cancer (67%), and lung cancer (12%). Testing rates and documentation mutational subtypes increased over time. Reporting of wildtype results varied between lung and colorectal cancer, with underreporting in lung cancer. Regional variations in testing and reporting were observed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study highlights substantial progress in KRAS and BRAF testing in Denmark from 2010 to 2022, evidenced by increased and more specific reporting of mutational test results, thereby improving the precision of cancer diagnosis and treatment. However, persistent regional variations and limited testing for cancer types beyond melanoma, colorectal, and lung cancer highlight the necessity for a nationwide assessment of the optimal testing approach.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23236","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140639510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel t(X;21)(p11.4;q22.12) translocation adds to the role of BCOR and RUNX1 in myelodysplastic syndromes and acute myeloid leukemias","authors":"Elena Mavridou,&nbsp;Anair Graciela Lema Fernandez,&nbsp;Carlotta Nardelli,&nbsp;Valentina Pierini,&nbsp;Martina Quintini,&nbsp;Silvia Arniani,&nbsp;Danika Di Giacomo,&nbsp;Barbara Crescenzi,&nbsp;Caterina Matteucci,&nbsp;Constantina Sambani,&nbsp;Cristina Mecucci","doi":"10.1002/gcc.23235","DOIUrl":"https://doi.org/10.1002/gcc.23235","url":null,"abstract":"<p>In myeloid neoplasms, both fusion genes and gene mutations are well-established events identifying clinicopathological entities. In this study, we present a thus far undescribed t(X;21)(p11.4;q22.12) in five cases with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The translocation was isolated or accompanied by additional changes. It did not generate any fusion gene or gene deregulation by aberrant juxtaposition with regulatory sequences. Molecular analysis by targeted next-generation sequencing showed that the translocation was accompanied by at least one somatic mutation in <i>TET2</i>, <i>EZH2</i>, <i>RUNX1</i>, <i>ASXL1</i>, <i>SRSF2</i>, <i>ZRSR2</i>, <i>DNMT3A</i>, and <i>NRAS</i> genes. Co-occurrence of deletion of <i>RUNX1</i> in 21q22 and of <i>BCOR</i> in Xp11 was associated with t(X;21). <i>BCOR</i> haploinsufficiency corresponded to a significant hypo-expression in t(X;21) cases, compared to normal controls and to normal karyotype AML. By contrast, <i>RUNX1</i> expression was not altered, suggesting a compensatory effect by the remaining allele. Whole transcriptome analysis showed that overexpression of <i>HOXA9</i> differentiated t(X;21) from both controls and t(8;21)-positive AML. In conclusion, we characterized a new recurrent reciprocal t(X;21)(p11.4;q22.12) chromosome translocation in MDS and AML, generating simultaneous <i>BCOR</i> and <i>RUNX1</i> deletions rather than a fusion gene at the genomic level.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23235","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140639511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel MIR143HG::PLAG1 gene fusion identified in a rectal myxoid leiomyosarcoma","authors":"Shuanzeng Wei,&nbsp;Jianming Pei,&nbsp;Paul Belser,&nbsp;Teresa Lee,&nbsp;Jeffrey M. Farma,&nbsp;Arthur S. Patchefsky,&nbsp;Douglas B. Flieder,&nbsp;Elizabeth A. Montgomery","doi":"10.1002/gcc.23239","DOIUrl":"https://doi.org/10.1002/gcc.23239","url":null,"abstract":"<p>Myxoid leiomyosarcoma (MLS) is a rare but well-documented tumor that often portends a poor prognosis compared to the conventional leiomyosarcoma. This rare sarcoma has been reported in the uterus, external female genitalia, soft tissue, and other locations. However, a definite rectal MLS has not been reported. Recently five cases of MLS were reported to harbor <i>PLAG1</i> fusions (<i>TRPS1::PLAG1, RAD51B::PLAG1,</i> and <i>TRIM13::PLAG1</i>). In this report, we present a case of rectal MLS with a novel <i>MIR143HG::PLAG1</i> fusion detected by RNA next-generation sequencing.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140639512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles and interactions of tumor microenvironment components in medulloblastoma with implications for novel therapeutics","authors":"Hanjie Yang,&nbsp;Min Li,&nbsp;Yuhao Deng,&nbsp;Huantao Wen,&nbsp;Minjie Luo,&nbsp;Wangming Zhang","doi":"10.1002/gcc.23233","DOIUrl":"https://doi.org/10.1002/gcc.23233","url":null,"abstract":"<p>Medulloblastomas, the most common malignant pediatric brain tumors, can be classified into the wingless, sonic hedgehog (SHH), group 3, and group 4 subgroups. Among them, the SHH subgroup with the <i>TP53</i> mutation and group 3 generally present with the worst patient outcomes due to their high rates of recurrence and metastasis. A novel and effective treatment for refractory medulloblastomas is urgently needed. To date, the tumor microenvironment (TME) has been shown to influence tumor growth, recurrence, and metastasis through immunosuppression, angiogenesis, and chronic inflammation. Treatments targeting TME components have emerged as promising approaches to the treatment of solid tumors. In this review, we summarize progress in research on medulloblastoma microenvironment components and their interactions. We also discuss challenges and future research directions for TME-targeting medulloblastoma therapy.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140550126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FGFR1 fusions as a novel molecular driver in rhabdomyosarcoma","authors":"Henry de Traux De Wardin,&nbsp;Joanna Cyrta,&nbsp;Josephine K. Dermawan,&nbsp;Delphine Guillemot,&nbsp;Daniel Orbach,&nbsp;Isabelle Aerts,&nbsp;Gaelle Pierron,&nbsp;Cristina R. Antonescu","doi":"10.1002/gcc.23232","DOIUrl":"https://doi.org/10.1002/gcc.23232","url":null,"abstract":"<p>The wide application of RNA sequencing in clinical practice has allowed the discovery of novel fusion genes, which have contributed to a refined molecular classification of rhabdomyosarcoma (RMS). Most fusions in RMS result in aberrant transcription factors, such as <i>PAX3</i>/<i>7::FOXO1</i> in alveolar RMS (ARMS) and fusions involving <i>VGLL2</i> or <i>NCOA2</i> in infantile spindle cell RMS. However, recurrent fusions driving oncogenic kinase activation have not been reported in RMS. Triggered by an index case of an unclassified RMS (overlapping features between ARMS and sclerosing RMS) with a novel <i>FGFR1::ANK1</i> fusion, we reviewed our molecular files for cases harboring <i>FGFR1</i>-related fusions. One additional case with an <i>FGFR1::TACC1</i> fusion was identified in a tumor resembling embryonal RMS (ERMS) with anaplasia, but with no pathogenic variants in <i>TP53</i> or <i>DICER1</i> on germline testing. Both cases occurred in males, aged 7 and 24, and in the pelvis. The 2nd case also harbored additional alterations, including somatic <i>TP53</i> and <i>TET2</i> mutations. Two additional RMS cases (one unclassified, one ERMS) with <i>FGFR1</i> overexpression but lacking <i>FGFR1</i> fusions were identified by RNA sequencing. These two cases and the <i>FGFR1::TACC1</i>-positive case clustered together with the ERMS group by RNAseq. This is the first report of RMS harboring recurrent <i>FGFR1</i> fusions. However, it remains unclear if <i>FGFR1</i> fusions define a novel subset of RMS or alternatively, whether this alteration can sporadically drive the pathogenesis of known RMS subtypes, such as ERMS. Additional larger series with integrated genomic and epigenetic datasets are needed for better subclassification, as the resulting oncogenic kinase activation underscores the potential for targeted therapy.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140546657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adolescent presentation of FGFR1::EBF2 gene fusion mesenchymal tumor","authors":"Omar Jaber,&nbsp;Iyad Sultan","doi":"10.1002/gcc.23234","DOIUrl":"https://doi.org/10.1002/gcc.23234","url":null,"abstract":"","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140541070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spindle cell neoplasms with novel LTK fusion – Expanding the spectrum of kinase fusion-positive soft tissue tumors","authors":"Maximus C. F. Yeung,&nbsp;Josephine K. Dermawan,&nbsp;Anthony P. Y. Liu,&nbsp;Albert Y. L. Lam,&nbsp;Cristina R. Antonescu,&nbsp;Tony W. H. Shek","doi":"10.1002/gcc.23227","DOIUrl":"10.1002/gcc.23227","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Kinase fusion-positive soft tissue tumors represent an emerging, molecularly defined group of mesenchymal tumors with a wide morphologic spectrum and diverse activating kinases. Here, we present two cases of soft tissue tumors with novel <i>LTK</i> fusions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>Both cases presented as acral skin nodules (big toe and middle finger) in pediatric patients (17-year-old girl and 2-year-old boy). The tumors measured 2 and 3 cm in greatest dimension. Histologically, both cases exhibited bland-looking spindle cells infiltrating adipose tissue and accompanied by collagenous stroma. One case additionally displayed perivascular hyalinization and band-like stromal collagen. Both cases exhibited focal S100 staining, and one case had patchy coexpression of CD34. Targeted RNA-seq revealed the presence of novel in-frame <i>MYH9::LTK</i> and <i>MYH10::LTK</i> fusions, resulting in upregulation of <i>LTK</i> expression. Of interest, DNA methylation-based unsupervised clustering analysis in one case showed that the tumor clustered with dermatofibrosarcoma protuberans (DFSP). One tumor was excised with amputation with no local recurrence or distant metastasis at 18-month follow-up. The other case was initially marginally excised with local recurrence after one year, followed by wide local excision, with no evidence of disease at 10 years of follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This is the first reported case series of soft tissue tumors harboring <i>LTK</i> fusion, expanding the molecular landscape of soft tissue tumors driven by activating kinase fusions. Furthermore, studies involving a larger number of cases and integrated genomic analyses will be warranted to fully elucidate the pathogenesis and classification of these tumors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23227","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}