Genes, Chromosomes & Cancer最新文献

{"title":"Uncovering the WWTR1::NCOA2 Gene fusion in low-grade myoepithelial-rich neoplasm with HMGA2 expression: A case report","authors":"Ziyad Alsugair,&nbsp;Daniel Pissaloux,&nbsp;Françoise Descotes,&nbsp;Franck Tirode,&nbsp;Jonathan Lopez,&nbsp;Jimmy Perrot,&nbsp;Ariane Lapierre,&nbsp;Maxime Fieux,&nbsp;Pierre Philouze,&nbsp;Anne Champagnac,&nbsp;Mihaela Onea,&nbsp;Nazim Benzerdjeb","doi":"10.1002/gcc.23244","DOIUrl":"10.1002/gcc.23244","url":null,"abstract":"<p>We describe a case of a pleomorphic adenoma (PA) arising from the para-tracheal accessory salivary gland in a 44-year-old male harboring a novel <i>WWTR1::NCOA2</i> gene fusion. To our knowledge, this novel gene fusion has not been described previously in salivary gland tumors. The patient presented with hoarseness of voice. The radiological exam revealed a mass in the upper third of the trachea involving the larynx. Histologically, the tumor consisted of bland-looking monocellular eosinophilic epithelial cells arranged in cords and sheets separated by thin fibrous stroma, focally forming a pseudo-tubular pattern. In immunohistochemistry, the tumor cells demonstrated positivity for CK7, PS100, SOX10, and HMGA2; and negativity for CK5/6, p40 p63, and PLAG1. In addition, the clustering analysis clearly demonstrates a clustering of tumors within the PA group. In addition to reporting this novel fusion in the PA spectrum, we discuss the relevant differential diagnoses and briefly review of <i>NCOA2</i> and <i>WWTR1</i> gene functions in normal and neoplastic contexts.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 5","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23244","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921883","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":"Metastasizing aneurysmal dermatofibroma initially diagnosed as angiosarcoma confirmed by CD63::PRKCD fusion gene detection with nanopore sequencing","authors":"Naoki Takeda,&nbsp;Naohiro Makise,&nbsp;Jason Lin,&nbsp;Hajime Kageyama,&nbsp;Mariko Oikawa,&nbsp;Takahiro Sugiyama,&nbsp;Hidetada Kawana,&nbsp;Akinobu Araki,&nbsp;Toshinori Tuskanishi,&nbsp;Hideyuki Kinoshita,&nbsp;Yoko Hagiwara,&nbsp;Hiroto Kamoda,&nbsp;Toru Motoi,&nbsp;Tsukasa Yonemoto,&nbsp;Masahito Kawazu,&nbsp;Makiko Itami","doi":"10.1002/gcc.23246","DOIUrl":"10.1002/gcc.23246","url":null,"abstract":"<p>Dermatofibroma (DF) is a benign tumor that forms pedunculated lesions ranging in size from a few millimeters to 2 cm, usually affecting the extremities and trunks of young adults. Histopathologically, DF is characterized by the storiform proliferation of monomorphic fibroblast-like spindle cells. In addition to neoplastic cells, secondary elements such as foamy histiocytes, Touton-type giant cells, lymphoplasmacytes, and epidermal hyperplasia are characteristic histological features. Several histological variants, including atypical, cellular, aneurysmal, and lipidized variants, have been reported; cases with variant histologies are sometimes misdiagnosed as sarcomas. We present a case of metastasizing aneurysmal DF that was initially diagnosed as an angiosarcoma on biopsy. A 26-year-old woman was referred to our hospital with a gradually enlarging subcutaneous mass in her lower left leg. Positron emission tomography-computed tomography revealed high fluorodeoxyglucose uptake not only in the tumor but also in the left inguinal region. On biopsy, ERG and CD31-positive atypical spindle cells proliferated in slit-like spaces with extravasation, leading to the diagnosis of angiosarcoma. Histology of the wide-resection specimen was consistent with DF, and lymph node metastasis was also observed. Nanopore DNA sequencing detected <i>CD63::PRKCD</i> fusion and copy number gain, although CD63 was not included in the target region of adaptive sampling. This report highlights the importance of recognizing the unusual clinical, radiological, and pathological features of DF to avoid misdiagnosis, and the potential diagnostic utility of nanopore sequencer.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 5","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921882","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":"Constitutional and acquired genetic variants in ARID5B in pediatric B-cell precursor acute lymphoblastic leukemia","authors":"Charlotte Ragnarsson,&nbsp;Minjun Yang,&nbsp;Larissa Helena Moura-Castro,&nbsp;Efe Aydın,&nbsp;Rebeqa Gunnarsson,&nbsp;Linda Olsson-Arvidsson,&nbsp;Henrik Lilljebjörn,&nbsp;Thoas Fioretos,&nbsp;Nicolas Duployez,&nbsp;Marketa Zaliova,&nbsp;Jan Zuna,&nbsp;Anders Castor,&nbsp;Bertil Johansson,&nbsp;Kajsa Paulsson","doi":"10.1002/gcc.23242","DOIUrl":"10.1002/gcc.23242","url":null,"abstract":"<p>Constitutional polymorphisms in <i>ARID5B</i> are associated with an increased risk of developing high hyperdiploid (HeH; 51–67 chromosomes) pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL). Here, we investigated constitutional and somatic <i>ARID5B</i> variants in 1335 BCP ALL cases from five different cohorts, with a particular focus on HeH cases. In 353 HeH ALL that were heterozygous for risk alleles and trisomic for chromosome 10, where <i>ARID5B</i> is located, a significantly higher proportion of risk allele duplication was seen for the SNPs rs7090445 (<i>p</i> = 0.009), rs7089424 (<i>p</i> = 0.005), rs7073837 (<i>p</i> = 0.03), and rs10740055 (<i>p</i> = 0.04). Somatic <i>ARID5B</i> deletions were seen in 16/1335 cases (1.2%), being more common in HeH than in other genetic subtypes (2.2% vs. 0.4%; <i>p</i> = 0.002). The expression of <i>ARID5B</i> in HeH cases with genomic deletions was reduced, consistent with a functional role in leukemogenesis. Whole-genome sequencing and RNA-sequencing in HeH revealed additional somatic events involving <i>ARID5B</i>, resulting in a total frequency of 3.6% of HeH cases displaying a somatic <i>ARID5B</i> aberration. Overall, our results show that both constitutional and somatic events in <i>ARID5B</i> are involved in the leukemogenesis of pediatric BCP ALL, particularly in the HeH subtype.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 5","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23242","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911988","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":"Osteoblastoma of the thumb with a novel PRSS44::ALK fusion and literature review of osteoblastoma of hands and feet bones","authors":"Andrew I. Brandea,&nbsp;Michelle Afkhami,&nbsp;Michael J. Klein,&nbsp;Diana Bell","doi":"10.1002/gcc.23241","DOIUrl":"10.1002/gcc.23241","url":null,"abstract":"<p>Osteoblastomas (OBs) are benign neoplasms constituting approximately 1% of primary bone tumors with a predilection for the spine and sacrum. We describe an OB of the proximal phalanx of the left thumb in a 38-year-old female. MRI of left hand demonstrated a 29-mm mildly expansile enhancing lesion involving the entire proximal phalanx of the first digit. Histology displayed a bone-forming tumor consisting of trabeculae of remodeled woven bone framed by plump osteoblasts in a vascularized background. Next-generation sequencing analysis identified a <i>PRSS44::ALK</i> fusion gene.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 5","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911991","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":"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}