Genes, Chromosomes & Cancer最新文献

{"title":"17p13 (TP53) Deletions Are Associated With an Aggressive Phenotype but Unrelated to Patient Prognosis in Urothelial Bladder Carcinomas","authors":"Martina Kluth,&nbsp;Melanie Hitzschke,&nbsp;Kira Furlano,&nbsp;Henning Plage,&nbsp;Sebastian Hofbauer,&nbsp;Sarah Weinberger,&nbsp;Bernhard Ralla,&nbsp;Annika Fendler,&nbsp;Michela de Martino,&nbsp;Florian Roßner,&nbsp;Simon Schallenberg,&nbsp;Sefer Elezkurtaj,&nbsp;Maximilian Lennartz,&nbsp;Andreas H. Marx,&nbsp;Henrik Samtleben,&nbsp;Margit Fisch,&nbsp;Michael Rink,&nbsp;Marcin Slojewski,&nbsp;Krystian Kaczmarek,&nbsp;Thorsten Ecke,&nbsp;Stefan Koch,&nbsp;Nico Adamini,&nbsp;Joachim Weischenfeldt,&nbsp;Tobias Klatte,&nbsp;Sarah Minner,&nbsp;Ronald Simon,&nbsp;Guido Sauter,&nbsp;Thorsten Schlomm,&nbsp;David Horst,&nbsp;Henrik Zecha","doi":"10.1002/gcc.23271","DOIUrl":"https://doi.org/10.1002/gcc.23271","url":null,"abstract":"<p>17p13 deletions including <i>TP53</i> and other genes represent a common cause for reduced/lost p53 function in tumor cells. In this study, we analyzed the impact of 17p13 (<i>TP53</i>) deletions and p53 expression on tumor aggressiveness and patient prognosis in urothelial carcinoma. The 17p13 copy number status was analyzed by fluorescence in situ hybridization (FISH) on more than 2700 urothelial bladder carcinomas in a tissue microarray format. 17p13 deletion data were compared to p53 expression data measured by immunohistochemistry (IHC) in a previous study. Different types of p53 alterations were compared with tumor phenotype and clinical outcome data. Deletions of 17p13 occurred in 23% of 2185 analyzable carcinomas. The fraction of tumors with 17p13 deletions increased from pTa G2 low (9%) to pTa G3 (24%, <i>p</i> &lt; 0.0001). In muscle-invasive carcinomas, 17p13 deletions were associated with advanced pT stage (<i>p</i> = 0.0246), but unrelated to patient prognosis (<i>p</i> &gt; 0.5). 17p13 deletions were significantly related to p53 immunostaining (<i>p</i> = 0.0375). 17p13 deletions were most common in tumors with complete lack of p53 staining (31%), which supports the concept that many of these tumors have a complete loss of p53 function (p53 null phenotype). 17p13 deletions were also increased in tumors with high p53 staining (25%). In conclusion, 17p13 deletions were most commonly seen in p53 negative cancers, supporting their role as a cause for the p53 null phenotype in urothelial cancer. The association of 17p13 deletions with high grade and advanced pT stage may reflect increasing genomic instability going along with stage and grade progression.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23271","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142320821","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":"Spindle Cell Rhabdomyosarcoma of the Prostate With ZFP64::NCOA2 Fusion","authors":"Azfar Neyaz,&nbsp;Alessandro Furlan,&nbsp;Arivarasan Karunamurthy,&nbsp;Ivy John","doi":"10.1002/gcc.23274","DOIUrl":"https://doi.org/10.1002/gcc.23274","url":null,"abstract":"","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142320819","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":"Diagnostic and Therapeutic Implications of a FUS::TFCP2 Fusion and ALK Activation in a Metastatic Rhabdomyosarcoma","authors":"Veronika Csizmok,&nbsp;Cameron J. Grisdale,&nbsp;Laura M. Williamson,&nbsp;Howard J. Lim,&nbsp;Lawrence Lee,&nbsp;Daniel J. Renouf,&nbsp;Steven J. M. Jones,&nbsp;Marco A. Marra,&nbsp;Janessa Laskin,&nbsp;Alannah Smrke","doi":"10.1002/gcc.23259","DOIUrl":"https://doi.org/10.1002/gcc.23259","url":null,"abstract":"<p>The identification of gene fusions in rare sarcoma subtypes can have diagnostic, prognostic, and therapeutic impacts for advanced cancer patients. Here, we present a case of a 31-year-old male with a lytic lesion of the left mandible initially diagnosed as an osteosarcoma but found to have a TFCP2 fusion and ALK alteration, redefining the diagnosis and providing rationale for a novel treatment strategy. Histologically, the tumor displayed hypercellular, spindled to epithelioid neoplasm and nuclear pleomorphism, while immunohistochemistry showed diffuse SATB2 and focal desmin staining. Whole genome and transcriptome analysis revealed a <i>FUS::TFCP2</i> fusion, the defining alteration of a rare molecularly characterized subtype of soft tissue sarcoma termed intraosseous rhabdomyosarcoma. An internal ALK deletion and extremely high ALK RNA expression were also identified, suggesting potential benefit of an ALK inhibitor. This patient displayed a rapid and dramatic clinical and radiographic response to an ALK inhibitor, alectinib. Unfortunately, the response was short-lived, likely due to the advanced stage and aggressiveness of the disease. This report describes genome and transcriptome characterization of an intraosseous rhabdomyosarcoma, few of which exist in the literature, as well as providing evidence that inhibition of ALK may be a rational treatment strategy for patients with this exceedingly rare soft tissue sarcoma subtype characterized by TFCP2 fusions and ALK activation.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23259","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142273235","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":"Comprehensive Analysis of Juvenile Nasopharyngeal Angiofibromas via Whole-Exome Sequencing","authors":"Kiran Kumari,&nbsp;Shariya Afroj,&nbsp;Deeksha Madhry,&nbsp;Yash Verma,&nbsp;Arvind K. Kairo,&nbsp;Alok Thakar,&nbsp;Kapil Sikka,&nbsp;Hitesh Verma,&nbsp;Bhupendra Verma","doi":"10.1002/gcc.23265","DOIUrl":"https://doi.org/10.1002/gcc.23265","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The molecular basis and mechanisms of juvenile nasopharyngeal angiofibromas (JNA) pathogenesis are still unknown. Despite being a rare and benign neoplasm, JNA is a locally aggressive and potentially destructive head and neck neoplasm, typically found in young males. The advancement of genome technologies and analytical tools has provided an unparalleled opportunity to explore the intricacy of JNA. The present study provides the first evidence of the involvement of Y-chromosome genes in JNA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 13 JNA patients at an advanced disease stage and five age-matched male controls were registered for this study. Whole-exome sequencing (WES) analysis was conducted followed by functional analysis to understand the molecular mechanism of the JNA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>WES analysis revealed a high prevalence of mutations in 14 genes within the protein-coding, male-specific region of the Y-chromosome of young males (mean age: 13.8 ± 2.4) with JNA. These mutations, occurring at 28 distinct positions, were characterized as moderate to high impact and were prevalent in nine JNA patients but not in the control group. The most frequently mutated genes were USP9Y and UTY, followed by KDM5D, DDX3Y, and TSPY4. The expression of USP9Y, UTY, and DDX3Y was found to be co-modulated, implying their coordinated regulation as a complex. Furthermore, somatic mutations were detected in genes previously linked to JNA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The wide array of genetic mutations in the Y-chromosome male-specific region, along with the somatic alterations identified in JNA, provides novel insights into JNA pathophysiology.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275082","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":"Low-Level BCR::ABL1 Transcript at Diagnosis in Childhood Leukemia: A 10-Year Single Institution Study","authors":"Lucy E. Cain,&nbsp;Oksana Mirochnik,&nbsp;Michael M. Stevens,&nbsp;Stewart J. Kellie,&nbsp;Bhavna Padhye,&nbsp;Steven J. Keogh,&nbsp;Dinisha Govender,&nbsp;Jessica Ryan,&nbsp;Luciano Dalla-Pozza,&nbsp;Caroline M. Bateman","doi":"10.1002/gcc.23269","DOIUrl":"https://doi.org/10.1002/gcc.23269","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) is a high risk form of ALL associated with dismal outcomes in the pre-tyrosine kinase inhibitor (TKI) era. Addition of a TKI to chemotherapy improves outcomes. Therefore, testing for the presence of the Philadelphia chromosome by at least two methods at the time of diagnosis is critical. Diagnostic testing may include karyotype, fluorescent in situ hybridisation (FISH), and RT-PCR for the <i>BCR</i>::<i>ABL1</i> transcript. The significance of low-level <i>BCR</i>::<i>ABL1</i> transcript by RT-PCR in the absence of the Philadelphia chromosome on karyotype or by FISH is unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This is a retrospective review of children diagnosed with acute leukemia at our institution from 2010 to 2020. Those positive for the <i>BCR</i>::<i>ABL1</i> transcript by qualitative RT-PCR, and negative for t(9;22) by karyotype or FISH were analyzed for demographics, cytogenetic and molecular features at diagnosis and relapse, treatment and outcomes. The Kaplan–Meier method was used to estimate event-free and overall survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Forty-seven of 306 (15%) patients with Ph- ALL had low-level <i>BCR</i>::<i>ABL1</i> detected by RT-PCR. Most (77%) had B-cell ALL. The e1a2 transcript was detected most frequently, in 43 (91%) patients. <i>BCR</i>::<i>ABL1</i> was quantifiable in 12/43 (28%) patients, with a median of 0.0008% (range 0.0003–0.095%). Seven patients (15%) relapsed. No patient with low-level <i>BCR</i>::<i>ABL1</i> at diagnosis developed Ph + ALL at relapse. There was no difference in 5-year event-free (77% versus 81%, <i>p</i> = 0.407) or overall survival (86% versus 91%, <i>p</i> = 0.3) between children with low-level <i>BCR</i>::<i>ABL1</i> (<i>n</i> = 47) and those without (<i>n</i> = 259).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p><i>BCR</i>::<i>ABL1</i> low-level positivity in children with newly diagnosed Ph- ALL is a relatively common finding and did not adversely affect outcome for patients treated using a contemporary risk-adapted approach.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142244821","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":"Comprehensive Analyses of Somatic Copy Number Alterations and Mutations Based on the Adenoma–Carcinoma Sequence","authors":"Tamotsu Sugai,&nbsp;Mitsumasa Osakabe,&nbsp;Noriyuki Uesugi,&nbsp;Wataru Habano,&nbsp;Naoki Yanagawa,&nbsp;Hiromu Suzuki","doi":"10.1002/gcc.23267","DOIUrl":"https://doi.org/10.1002/gcc.23267","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Identifying molecular alterations in the adenoma and carcinoma components within the same tumor would greatly contribute to understanding the neoplastic progression of early colorectal cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>We examined somatic copy number alterations (SCNAs) and mutations involved in the adenoma and carcinoma components obtained from the same tumor in 46 cases of microsatellite-stable carcinoma in adenoma, using a genome-wide SNP array and gene mutation panel. In addition, we also performed hierarchical clustering to determine the SCNA frequencies in the tumors, resulting in stratification of the samples into two subgroups according to SCNA frequency. Subgroup 1 was characterized by multiple SCNAs and carcinoma components exclusively, while Subgroup 2 was characterized by a low frequency of SCNAs and both the adenoma and carcinoma components. The numbers of total genes and genes with gains were higher in the carcinoma than adenoma components. The three most frequent gains in both components were located at 1p36.33–1q44, 2p25.3–2q37.3, and 3p26.3–3q29. However, no candidate genes mapped to these regions. <i>APC</i> and <i>KRAS</i> mutations were common in both components, whereas the frequency of <i>TP53</i> mutations was statistically higher in the carcinoma than adenoma component. However, <i>TP53</i> mutations were not correlated with SCNA frequency.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We suggest that considerable SCNAs and <i>TP53</i> mutations are required for progression from adenoma to carcinoma within the same intramucosal neoplastic lesion.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23267","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170133","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":"Molecular Analysis of Renal/Adrenal Angiosarcomas Reveals High Frequency of Recurrent Genetic Alterations","authors":"Pedram Argani,&nbsp;Carla Saoud,&nbsp;Cristina R. Antonescu","doi":"10.1002/gcc.23268","DOIUrl":"10.1002/gcc.23268","url":null,"abstract":"<div>\u0000 \u0000 <p>Angiosarcomas of the kidney and adrenal gland are rare, highly aggressive vascular neoplasms. Their genomic profile has not been systematically studied to date. We report the clinicopathologic and molecular features of six angiosarcomas centered in the kidney/adrenal gland. All patients were male adults, ranging from 58 to 77 years of age. Tumor sizes ranged from 2.5 to 22.5 cm. Half of the cases demonstrated hot spot mutations in the <i>KDR</i> gene, while one-third demonstrated mutations in the <i>PIK3CA</i> gene; both of these gene alterations being previously described, preferentially in breast angiosarcomas. In addition, two cases each demonstrated <i>BRIP1</i> gene amplification, <i>CTNNB1</i> and <i>ETV6</i> mutations, which have not been previously reported in angiosarcoma. Notably, molecular studies were critical in establishing the correct diagnoses in three cases: one was an epithelioid angiosarcoma originally misdiagnosed as metastatic adenocarcinoma to the adrenal gland, the second was a vasoformative angiosarcoma that mimicked hemangioma, and the third was a collision tumor between a high-grade angiosarcoma and a chromophobe renal cell carcinoma which was originally diagnosed as a sarcomatoid renal cell carcinoma. In summary, angiosarcomas of the kidney and adrenal gland have a high frequency of recurrent genetic alterations, some of them being shared with other angiosarcoma subtypes, while other appear to be novel. In particular, activating hot spot <i>KDR</i> and <i>PIK3CA</i> mutations represent potential therapeutic targets for these highly aggressive cancers.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153746","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":"Pediatric Fibromatosis Lacks the Internal Tandem Duplication of EGFR Seen in Congenital Mesoblastic Nephroma","authors":"Rose Chami,&nbsp;Paula Marrano,&nbsp;Paul S. Thorner","doi":"10.1002/gcc.23266","DOIUrl":"10.1002/gcc.23266","url":null,"abstract":"<p>Classical and mixed congenital mesoblastic nephroma (CMN) are characterized by an internal tandem duplication (ITD) of the <i>EGFR</i> gene, in contrast to cellular CMN that usually harbors an <i>ETV6::NTRK3</i> gene fusion. This same fusion occurs in infantile fibrosarcoma, and this tumor can be considered as the soft tissue equivalent of cellular CMN. A soft tissue equivalent of classic/mixed CMN remains undefined at the genetic level. Since classical CMN resembles fibromatosis of soft tissue histologically, we asked whether fibromatosis in children might show <i>EGFR</i> ITD. ITD was investigated using the polymerase chain reaction and primers for exons 18 and 25 of the <i>EGFR</i> gene. Seven of the eight cases of classical or mixed CMN were positive by this approach, but none of the five cellular CMNs. Of 11 cases of fibromatosis (six plantar, two digital, and three desmoid), none were positive for <i>EGFR</i> ITD. Within the limits of this small study, we conclude that pediatric fibromatosis is likely not characterized by <i>EGFR</i> ITD. There are isolated reports of pediatric soft tissue tumors that harbor <i>EGFR</i> ITD, but these have the appearance of infantile fibrosarcoma or mixed CMN rather than fibromatosis. We did not find any such cases, since all 14 cases of infantile fibrosarcoma in our study had an <i>ETV6::NTRK3</i> fusion. The soft tissue tumors with <i>EGFR</i> ITD are not a morphologic match for the low-grade histology of classical CMN. Whether they have a similar favorable biology or behave more like fibrosarcoma with an <i>ETV6::NTRK3</i> fusion or an alternative fusion involving other kinases remains to be determined.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23266","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153747","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":"Gene Expression Profiles of AHNAK2, DCSTAMP, FN1, and TERT Correlate With Mutational Status and Recurrence in Papillary Thyroid Carcinoma","authors":"Julia I. Staubitz-Vernazza,&nbsp;Celine Müller,&nbsp;Antonia Heymans,&nbsp;Annekathrin Silvia Nedwed,&nbsp;Mario Schindeldecker,&nbsp;Monika Hartmann,&nbsp;Michael Kloth,&nbsp;Arno Schad,&nbsp;Wilfried Roth,&nbsp;Thomas J. Musholt,&nbsp;Nils Hartmann","doi":"10.1002/gcc.23256","DOIUrl":"10.1002/gcc.23256","url":null,"abstract":"<p>Papillary thyroid carcinoma (PTC), the most common malignancy of follicular cell derivation, is generally associated with good prognosis. Nevertheless, it is important to identify patients with aggressive PTCs and unfavorable outcome. Molecular markers such as <i>BRAF</i>^<i>V600E</i> mutation and <i>TERT</i> promoter mutations have been proposed for risk stratification. While <i>TERT</i> promoter mutations have been frequently associated with aggressive PTCs, the association of <i>BRAF</i>^<i>V600E</i> mutation with increased recurrence and mortality is less clear and has been controversially discussed. The aim of the present study was to analyze whether differentially expressed genes can predict <i>BRAF</i>^<i>V600E</i> mutations as well as <i>TERT</i> promoter mutations in PTCs. RNA sequencing identified a large number of differentially expressed genes between <i>BRAF</i>^<i>V600E</i> and <i>BRAF</i>^{<i>wildtype</i>} PTCs. Of those, <i>AHNAK2</i>, <i>DCSTAMP</i>, and <i>FN1</i> could be confirmed in a larger cohort (<i>n</i> = 91) to be significantly upregulated in <i>BRAF</i>^<i>V600E</i> mutant PTCs using quantitative RT-PCR. Moreover, individual PTC expression values of <i>DCSTAMP</i> and <i>FN1</i> were able to predict the <i>BRAF</i>^<i>V600E</i> mutation status with high sensitivity and specificity. The expression of <i>TERT</i> was detected in all PTCs harboring <i>TERT</i> promoter mutations and in 19% of PTCs without <i>TERT</i> promoter mutations. Tumors with both <i>TERT</i> expression and <i>TERT</i> promoter mutations were particularly associated with aggressive clinicopathological features and a shorter recurrence-free survival. Altogether, it will be interesting to explore the biological function of <i>AHNAK2</i>, <i>DCSTAMP</i>, and <i>FN1</i> in PTC in more detail. The analysis of their expression patterns could allow the characterization of PTC subtypes and thus enabling a more individualized surgical and medical treatment.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23256","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080110","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":"Structural Variants in the SMC1A Gene Associated With Near-Haploidy in Undifferentiated Pleomorphic Sarcomas","authors":"Sebastian Ibstedt,&nbsp;Paul Piccinelli,&nbsp;Saskia Sydow,&nbsp;Jan Köster,&nbsp;Fredrik Mertens","doi":"10.1002/gcc.23255","DOIUrl":"10.1002/gcc.23255","url":null,"abstract":"<div>\u0000 \u0000 <p>Near-haploidization, that is, loss of one copy of most chromosomes, is a relatively rare phenomenon in most tumors, but is enriched among certain soft tissue sarcomas, including undifferentiated pleomorphic sarcoma (UPS). Presumably, near-haploidization can arise through many mechanisms. This study aimed to identify gene rearrangements that could cause near-haploidization. We here present two UPS in which near-haploidization was an early event, identified through single nucleotide polymorphism (SNP) array analysis. One of the cases was studied further using whole genome and transcriptome sequencing, as well as cytogenetic and molecular cytogenetic methods. Both tumors had chromosomal rearrangements in the form of copy number shifts/structural variants affecting the <i>SMC1A</i> gene. These findings suggest that cohesin defects could contribute to mitotic errors resulting in massive loss of chromosomes. <i>SMC1A</i> encodes one of the components of the cohesin multiprotein complex, which is critical for proper alignment of the sister chromatids during S-phase and separation to opposite spindle poles. Further studies should explore the role of cohesin defects in near-haploidization in other sarcomas and to clarify its role in tumor development.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987733","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}