Genes, Chromosomes & Cancer最新文献

{"title":"Aggressive Spindle Cell Sarcoma in Young Woman With the FGFR1::EBF2 Fusion","authors":"Harumi Nakamura, Yoji Kukita, Ken-ichi Yoshida, Hironari Tamiya, Shigeki Kadonaga, Satoshi Takenaka, Toshinari Yagi","doi":"10.1002/gcc.70000","DOIUrl":"https://doi.org/10.1002/gcc.70000","url":null,"abstract":"","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142449222","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":"Cell Senescence and the Genetics of Melanoma Development","authors":"Sophie M. Constantinou,&nbsp;Dorothy C. Bennett","doi":"10.1002/gcc.23273","DOIUrl":"https://doi.org/10.1002/gcc.23273","url":null,"abstract":"<p>Cutaneous malignant melanoma is an aggressive skin cancer with an approximate lifetime risk of 1 in 38 in the UK. While exposure to ultraviolet radiation is a key environmental risk factor for melanoma, up to ~10% of patients report a family history of melanoma, and ~1% have a strong family history. The understanding of causal mutations in melanoma has been critical to the development of novel targeted therapies that have contributed to improved outcomes for late-stage patients. Here, we review current knowledge of the genes affected by familial melanoma mutations and their partial overlap with driver genes commonly mutated in sporadic melanoma development. One theme linking a set of susceptibility loci/genes is the regulation of skin pigmentation and suntanning. The largest functional set of susceptibility variants, typically with high penetrance, includes <i>CDKN2A</i>, <i>RB1</i>, and telomerase reverse transcriptase (<i>TERT</i>) mutations, associated with attenuation of cell senescence. We discuss the mechanisms of action of these gene sets in the biology and progression of nevi and melanoma.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23273","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142449221","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":"Sporadic NF1-Mutated Inflammatory Polyps of the Colon: A Case Report and Brief Literature Review","authors":"Azfar Neyaz,&nbsp;Ibrahim Abukhiran,&nbsp;Rana Naous","doi":"10.1002/gcc.70001","DOIUrl":"https://doi.org/10.1002/gcc.70001","url":null,"abstract":"","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451212","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":"Potential Use of Extracellular Vesicles for the HER2 Status Assessment in Breast Cancer Patients","authors":"Sol Moon,&nbsp;Seung Il Kim,&nbsp;Suji Lee,&nbsp;Hyojung Lee,&nbsp;Young Kim,&nbsp;Joon Ye Kim,&nbsp;Min Woo Kim,&nbsp;Jee Ye Kim","doi":"10.1002/gcc.23264","DOIUrl":"https://doi.org/10.1002/gcc.23264","url":null,"abstract":"<p>Human epithelial growth factor receptor 2 (HER2)-targeted therapies are effective in patients with HER2-positive breast cancer. Recent advances have shown that HER2-targeted therapies can also be of benefit when treating tumors expressing low levels of HER2, highlighting the importance of identifying the HER2-low subgroup. This clinical trend has opened new therapeutic avenues for patients who were previously ineligible for HER2-targeted therapies. Thus, the development of new diagnostic methods for real-time HER2 profiling is crucial for accurately tailoring the treatment for these patients. We hypothesized that tumor-derived extracellular vesicles (TEVs) could reflect the HER2 profiles of primary tumors and potentially serve as diagnostic tools for HER2 status. This approach was validated using six breast cancer cell lines, which confirmed that the TEVs accurately reflected the HER2 profiles of the tumor cells. TEVs were isolated using an immunoaffinity method, and copy number variation (CNV) in the <i>ERBB2/EIF2C</i> ratio was assessed using droplet digital PCR of DNA from these vesicles. Clinical validation using plasma samples from 33 breast cancer patients further reinforced the diagnostic potential of our method. Pearson's correlation coefficient analysis of the flow cytometry results demonstrated that TEVs reflected HER2 expression in primary cells. To distinguish between HER2-negative and HER2-low patients, the area under the curve (AUC) of the ROC curve in our method was 0.796, with a sensitivity of 53.8% and a specificity of 100%. These findings suggest the clinical utility of extracellular vesicles derived from plasma and emphasize the need for further research to distinguish HER2-negative from HER2-low patients.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23264","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443476","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 Profiling of Low-Grade Appendiceal Mucinous Neoplasms (LAMN)","authors":"Julia Doll,&nbsp;Katja Maurus,&nbsp;Franziska Köhler,&nbsp;Niels Matthes,&nbsp;Johan F. Lock,&nbsp;Christoph-Thomas Germer,&nbsp;Andreas Rosenwald,&nbsp;Armin Wiegering","doi":"10.1002/gcc.23270","DOIUrl":"https://doi.org/10.1002/gcc.23270","url":null,"abstract":"<p>Low-grade appendiceal mucinous neoplasia (LAMN) represents a relatively rare tumor of the appendix typically diagnosed incidentally through appendectomy for acute appendicitis. In cases where perforation occurs, mucinous content may disseminate into the abdominal cavity, leading to the development of pseudomyxoma peritonei (PMP). The primary objective of this study was to elucidate the molecular characteristics associated with various stages of LAMN and PMP. DNA was extracted from LAMN, primary PMPs, recurrent PMPs, and adenocarcinomas originating from LAMN. The subsequent analysis involved the examination of mutational hotspot regions within 50 cancer-related genes, covering over 2800 COSMIC mutations, utilizing amplicon-based next-generation sequencing (NGS). Our findings revealed activating somatic mutations within the MAPK-signaling pathway across all tumors examined. Specifically, 98.1% of cases showed mutations in <i>KRAS</i>, while one tumor harbored a <i>BRAF</i> mutation. Additionally, <i>GNAS</i> mutations were identified in 55.8% of tumors, with no significant difference observed between LAMN and PMP. While LAMN rarely displayed additional mutations, 42% of primary PMPs and 60% of recurrent PMPs showed additional mutations. Notably, both adenocarcinomas originating from LAMN showed mutations within <i>TP53</i>. Furthermore, 7.7% (4/52) of cases exhibited a potentially targetable <i>KRAS</i> G12C mutation. In four patients, NGS analysis was performed on both primary PMP and recurrent PMP/adenocarcinoma samples. While mutations in <i>KRAS</i> and <i>GNAS</i> were detected in almost all samples, 50% of recurrent cases displayed an additional <i>SMAD4</i> mutation, suggesting a notable alteration during disease progression. Our findings indicate two key points: First, mutations within the MAPK pathway, particularly in <i>KRAS</i>, are evident across all tumors, along with a high frequency of <i>GNAS</i> mutations. Second, progression toward PMP or adenocarcinoma is associated with an accumulation of additional mutations within common oncogenic pathways.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23270","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435482","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":"Establishment and Characterization of a Novel Pleuropulmonary Blastoma Cell Line","authors":"Keisuke Kato,&nbsp;Hiroaki Goto,&nbsp;Mio Tanaka,&nbsp;Tetsuomi Suzuki,&nbsp;Yasunori Toyoda,&nbsp;Masato Shinkai,&nbsp;Norihiko Kitagawa,&nbsp;Toshiji Nishi,&nbsp;Hisato Kigasawa,&nbsp;Kenji Kurosawa,&nbsp;Noriko Aida,&nbsp;Ai Yoshimi,&nbsp;Asami Noda,&nbsp;Yumi Ito,&nbsp;Masafumi Seki,&nbsp;Junko Takita,&nbsp;Noriyuki Nagahara,&nbsp;Masahiro Tsuchida,&nbsp;Yukichi Tanaka","doi":"10.1002/gcc.23276","DOIUrl":"https://doi.org/10.1002/gcc.23276","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Pleuropulmonary blastoma (PPB) is an infrequently encountered childhood malignant intrathoracic neoplasm associated with unfavorable clinical behavior. Since a well-characterized preclinical model is essential for developing competent agents for PPB, we aim to establish and characterize the world's first cell line of PPB, and attempt to perform the cytotoxicity assay on the PPB cell line.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Experimental Design</h3>\u0000 \u0000 <p>The index case is a 2-year-old female who developed a right thoracic tumor that was surgically removed and treated with multi-agent chemotherapy. The patient is free from recurrence, although it was 9 years after the diagnosis when she developed a thyroid tumor. We performed in vitro cultivation of the isolated neoplastic cells from the tumor, cytogenetic findings and molecular analysis, and tetrazolium colorimetric assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>The histology was consistent with PPB. Serial passage of cultivation produced a continuously growing cell line, KCMC-PPB-1. Conventional cytogenetic analysis of the established cell line revealed complex numerical and structural chromosomal abnormalities, including add(17)(p11). Mutation analysis on the cultured cells revealed amino-acid substitution mutation on exon 4 of <i>TP53</i> (NM_001276760.3:c.212_213delTG; NP_001263689.1:p.Leu72ArgfsTer37) and compound heterozygous mutations of <i>DICER1</i> (NM_177438.3:c. 4910C&gt;A; NP_803187.1:Ser1637* and NM_177438.3:c. 5114A&gt;T; NP_803187.1:Glu1705Val). The cultivated cells demonstrated vulnerability to bortezomib on cytotoxicity assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our KCMC-PPB-1 is the first genuine, molecularly characterized PPB cell line. The cell line is transplantable to nu/nu mice; therefore, it is suitable for a preclinical model for new drug development. The cytotoxicity assay demonstrated that bortezomib is active in the current PPB model.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435481","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":"MYH9::LTK Fusion in a Pediatric Acral Soft Tissue Spindle Cell Neoplasm","authors":"Larissa V. Furtado,&nbsp;Ana C. Polanco,&nbsp;Zonggao Shi,&nbsp;Soad Fuentes-Alabi,&nbsp;Roxana Martinez,&nbsp;Alberto Pappo,&nbsp;Teresa Santiago","doi":"10.1002/gcc.23277","DOIUrl":"https://doi.org/10.1002/gcc.23277","url":null,"abstract":"","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142429985","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":"RUNX1::MIR99AHG Chimera in Acute Myeloid Leukemia","authors":"Kristin Andersen,&nbsp;Geir E. Tjønnfjord,&nbsp;L. Frode Ramslien,&nbsp;Ioannis Panagopoulos","doi":"10.1002/gcc.23272","DOIUrl":"https://doi.org/10.1002/gcc.23272","url":null,"abstract":"<p><i>RUNX1</i> fuses with over 70 different partner genes in hematological neoplasms. While common <i>RUNX1</i> chimeras have been extensively studied and their prognosis is well established, our current understanding of less common <i>RUNX1</i> chimeras is limited. Here, we present a case of acute myeloid leukemia (AML) with a rare <i>RUNX1</i> chimera. Bone marrow cells obtained at diagnosis from a 71-year-old patient diagnosed with AML-M5 were studied using G-banding, fluorescence in situ hybridization, array comparative genomic hybridization, RNA sequencing, PCR, and Sanger sequencing. Combined findings from the abovementioned assays suggested three cytogenetic clones: one with a normal karyotype, one with inv(21)(q21q22), and one with two inv(21)(q21q22). The molecular analysis revealed the fusion of <i>RUNX1</i> with <i>MIR99AHG</i> (at 21q21.1), further supporting the presence of an inv(21)(q21q22). The present case is the third reported AML harboring a <i>RUNX1::MIR99AHG</i> chimera. Similar to the two previously described AML patients, our case also had an <i>FLT3</i> aberration.</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.23272","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142320769","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":"Prevalence and Reclassification of Genetic Variants in South African Populations with Breast Cancer","authors":"Tabitha S. Osler,&nbsp;Jean-Tristan Brandenburg,&nbsp;Mardelle Schoeman,&nbsp;Wenlong Carl Chen,&nbsp;Michael F. Urban,&nbsp;Christopher G. Mathew","doi":"10.1002/gcc.23275","DOIUrl":"https://doi.org/10.1002/gcc.23275","url":null,"abstract":"<p>Concurrent testing of numerous genes for hereditary breast cancer (BC) is available but can result in management difficulties. We evaluated use of an expanded BC gene panel in women of diverse South African ancestries and assessed use of African genomic data to reclassify variants of uncertain significance (VUS). A total of 331 women of White, Black African, or Mixed Ancestry with BC had a 9-gene panel test, with an additional 75 genes tested in those without a pathogenic/likely pathogenic (P/LP) variant. The proportion of VUS reclassified using ClinGen gene-specific allele frequency (AF) thresholds or an AF &gt; 0.001 in nonguidelines genes in African genomic data was determined. The 9-gene panel identified 58 P/LP variants, but only two of the P/LP variants detected using the 75-gene panel were in confirmed BC genes, resulting in a total of 60 (18.1%) in all participants. P/LP variant prevalence was similar across ancestry groups, but VUS prevalence was higher in Black African and Mixed Ancestry than in White participants. In total, 611 VUS were detected, representing 324 distinct variants. 10.8% (9/83) of VUS met ClinGen AF thresholds in genomic data while 10.8% (26/240) in nonguideline genes had an AF &gt; 0.001. Overall, 27.0% of VUS occurrences could potentially be reclassified using African genomic data. Thus, expanding the gene panel yielded few clinically actionable variants but many VUS, particularly in participants of Black African and Mixed Ancestry. However, use of African genomic data has the potential to reclassify a significant proportion of VUS.</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.23275","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142320820","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":"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}