Genes, Chromosomes & Cancer最新文献

{"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}

{"title":"Genetic Heterogeneity in Cellular Angiofibromas","authors":"Ioannis Panagopoulos,&nbsp;Kristin Andersen,&nbsp;Ingvild Lobmaier,&nbsp;Marius Lund-Iversen","doi":"10.1002/gcc.23262","DOIUrl":"10.1002/gcc.23262","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cellular angiofibroma, a rare benign mesenchymal neoplasm, is classified within the 13q/RB1 family of tumors due to morphological, immunohistochemical, and genetic similarities with spindle cell lipoma. Here, genetic data reveal pathogenetic heterogeneity in cellular angiofibroma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Three cellular angiofibromas were studied using G-banding/Karyotyping, array comparative genomic hybridization, RNA sequencing, and direct cycling sequencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The first tumor carried a del(13)(q12) together with heterozygous loss and minimal expression of the <i>RB1</i> gene. Tumors two and three displayed chromosome 8 abnormalities associated with chimeras of the pleomorphic adenoma gene 1 (<i>PLAG1</i>). In tumor 2, the cathepsin B (<i>CTSB</i>) fused to <i>PLAG1</i> (<i>CTSB::PLAG1</i>) while in tumor 3, the mir-99a-let-7c cluster host gene (<i>MIR99AHG</i>) fused to <i>PLAG1</i> (<i>MIR99AHG::PLAG1</i>), both leading to elevated expression of <i>PLAG1</i> and insulin growth factor 2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study uncovers two genetic pathways contributing to the pathogenetic heterogeneity within cellular angiofibromas. The first aligns with the 13q/RB1 family of tumors and the second involves <i>PLAG1</i>-chimeras. These findings highlight the diverse genetic landscape of cellular angiofibromas, providing insights into potential diagnostic strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23262","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906400","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":"Hereditary Colorectal Cancer and Polyposis Syndromes Caused by Variants in Uncommon Genes","authors":"Ahmed Bouras,&nbsp;Aurélie Fabre,&nbsp;Hélène Zattara,&nbsp;Sandrine Handallou,&nbsp;Françoise Desseigne,&nbsp;Caroline Kientz,&nbsp;Fabienne Prieur,&nbsp;Magalie Peysselon,&nbsp;Clémentine Legrand,&nbsp;Laura Calavas,&nbsp;Jean-Christophe Saurin,&nbsp;Qing Wang","doi":"10.1002/gcc.23263","DOIUrl":"10.1002/gcc.23263","url":null,"abstract":"<p>A substantial number of hereditary colorectal cancer (CRC) and colonic polyposis cannot be explained by alteration in confirmed predisposition genes, such as mismatch repair (MMR) genes, <i>APC</i> and <i>MUTYH</i>. Recently, a certain number of potential predisposition genes have been suggested, involving each a small number of cases reported so far. Here, we describe the detection of rare variants in the <i>NTLH1</i>, <i>AXIN2</i>, <i>RNF43</i>, <i>BUB1</i>, and <i>TP53</i> genes in nine unrelated patients who were suspected for inherited CRC and/or colonic polyposis. Seven of them were classified as pathogenic or likely pathogenic variants (PV/LPV). Clinical manifestations of carriers were largely consistent with reported cases with, nevertheless, distinct characteristics. PV/LPV in these uncommon gene can be responsible for up to 2.7% of inherited CRC or colonic polyposis syndromes. Our findings provide supporting evidence for the role of these genes in cancer predisposition, and contribute to the determination of related cancer spectrum and cancer risk for carriers, allowing for the establishment of appropriate screening strategy and genetic counseling in affected families.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23263","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906401","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":"TLE3 Is a Novel Fusion Partner of JAK2 in Myeloid/Lymphoid Neoplasm With Eosinophilia Responding to JAK2 Inhibition","authors":"Vladimir Lazarevic,&nbsp;Henrik Lilljebjörn,&nbsp;Linda Olsson-Arvidsson,&nbsp;Christina Orsmark-Pietras,&nbsp;Helena Ågerstam","doi":"10.1002/gcc.23261","DOIUrl":"10.1002/gcc.23261","url":null,"abstract":"<p>Chromosomal rearrangements involving Janus kinase 2 (<i>JAK2</i>) are rare but recurrent findings in lymphoid or myeloid neoplasia. Detection of <i>JAK2</i> fusion genes is important as patients with aberrantly activated JAK2 may benefit from treatment with tyrosine kinase inhibitors such as ruxolitinib. Here, we report a novel fusion gene between the transcriptional co-repressor-encoding gene transducin-like enhancer of split 3 (<i>TLE3)</i> and <i>JAK2</i> in a patient initially diagnosed with chronic eosinophilic leukemia with additional mutations in <i>PTPN11</i> and <i>NRAS</i>. The patient was successfully treated with the JAK2 inhibitor ruxolitinib for 8 months before additional somatic mutations were acquired and the disease progressed into an acute lymphoblastic T-cell leukemia/lymphoma. The present case shows similarities to previously reported cases with <i>PCM1::JAK2</i> and <i>BCR::JAK2</i> with regard to disease phenotype and response to ruxolitinib, and importantly, provides an example that also patients harboring other <i>JAK2</i> fusion genes may benefit from treatment with JAK2 inhibitors.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23261","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893252","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":"Precision Diagnostics in Myeloid Malignancies: Development and Validation of a National Capture-Based Gene Panel","authors":"Christina Orsmark-Pietras,&nbsp;Anna Lyander,&nbsp;Claes Ladenvall,&nbsp;Björn Hallström,&nbsp;Anna Staffas,&nbsp;Hero Awier,&nbsp;Aleksandra Krstic,&nbsp;Panagiotis Baliakas,&nbsp;Gisela Barbany,&nbsp;Cecilia Brunhoff Håkansson,&nbsp;Anna Gellerbring,&nbsp;Anna Hagström,&nbsp;Eva Hellström-Lindberg,&nbsp;Gunnar Juliusson,&nbsp;Vladimir Lazarevic,&nbsp;Arielle Munters,&nbsp;Tatjana Pandzic,&nbsp;Mia Wadelius,&nbsp;Joel Ås,&nbsp;Linda Fogelstrand,&nbsp;Valtteri Wirta,&nbsp;Richard Rosenquist,&nbsp;Lucia Cavelier,&nbsp;Thoas Fioretos,&nbsp;the SciLifeLab Clinical Genomics Platform and Genomic Medicine Sweden","doi":"10.1002/gcc.23257","DOIUrl":"https://doi.org/10.1002/gcc.23257","url":null,"abstract":"<p>Gene panel sequencing has become a common diagnostic tool for detecting somatically acquired mutations in myeloid neoplasms. However, many panels have restricted content, provide insufficient sensitivity levels, or lack clinically validated workflows. We here describe the development and validation of the Genomic Medicine Sweden myeloid gene panel (GMS-MGP), a capture-based 191 gene panel including mandatory genes in contemporary guidelines as well as emerging candidates. The GMS-MGP displayed uniform coverage across all targets, including recognized difficult GC-rich areas. The validation of 117 previously described somatic variants showed a 100% concordance with a limit-of-detection of a 0.5% variant allele frequency (VAF), achieved by utilizing error correction and filtering against a panel-of-normals. A national interlaboratory comparison investigating 56 somatic variants demonstrated highly concordant results in both detection rate and reported VAFs. In addition, prospective analysis of 323 patients analyzed with the GMS-MGP as part of standard-of-care identified clinically significant genes as well as recurrent mutations in less well-studied genes. In conclusion, the GMS-MGP workflow supports sensitive detection of all clinically relevant genes, facilitates novel findings, and is, based on the capture-based design, easy to update once new guidelines become available. The GMS-MGP provides an important step toward nationally harmonized precision diagnostics of myeloid malignancies.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 7","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23257","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141730281","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":"Loss of Chromosome Y in Neuroblastoma Is Associated With High-Risk Disease, 11q-Deletion, and Telomere Maintenance","authors":"Anna Djos,&nbsp;Johanna Svensson,&nbsp;Jennie Gaarder,&nbsp;Ganesh Umapathy,&nbsp;Staffan Nilsson,&nbsp;Torben Ek,&nbsp;Hartmut Vogt,&nbsp;Kleopatra Georgantzi,&nbsp;Ingrid Öra,&nbsp;Catarina Träger,&nbsp;Per Kogner,&nbsp;Tommy Martinsson,&nbsp;Susanne Fransson","doi":"10.1002/gcc.23260","DOIUrl":"https://doi.org/10.1002/gcc.23260","url":null,"abstract":"<p>Neuroblastoma (NB) is a heterogeneous childhood cancer with a slightly higher incidence in boys than girls, with the reason for this gender disparity unknown. Given the growing evidence for the involvement of loss of the Y chromosome (LoY) in male diseases including cancer, we investigated Y chromosome status in NB. Male NB tumor samples from a Swedish cohort, analyzed using Cytoscan HD SNP-microarray, were selected. Seventy NB tumors were analyzed for aneuploidy of the Y chromosome, and these data were correlated with other genetic, biological, and clinical parameters. LoY was found in 21% of the male NB tumors and it was almost exclusively found in those with high-risk genomic profiles. Furthermore, LoY was associated with increased age at diagnosis and enriched in tumors with 11q-deletion and activated telomere maintenance mechanisms. In contrast, tumors with an <i>MYCN</i>-amplified genomic profile retained their Y chromosome. The understanding of LoY in cancer is limited, making it difficult to conclude whether LoY is a driving event in NB or function of increased genomic instability. Gene expression analysis of Y chromosome genes in male NB tumors showed low expression of certain genes correlating with worse overall survival. <i>KDM5D</i>, encoding a histone demethylase stands out as an interesting candidate for further studies. LoY has been shown to impact the epigenomic layer of autosomal loci in nonreproductive tissues, and <i>KDM5D</i> has been reported as downregulated and/or associated with poor survival in different malignancies. Further studies are needed to explore the mechanisms and functional consequences of LoY in NB.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 7","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23260","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141730282","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":"The Variable Genomic Landscape During Osteosarcoma Progression: Insights From a Longitudinal WGS Analysis","authors":"Debora M. Meijer,&nbsp;Dina Ruano,&nbsp;Inge H. Briaire-de Bruijn,&nbsp;Pauline M. Wijers-Koster,&nbsp;Michiel A. J. van de Sande,&nbsp;Hans Gelderblom,&nbsp;Anne-Marie Cleton-Jansen,&nbsp;Noel F. C. C. de Miranda,&nbsp;Marieke L. Kuijjer,&nbsp;Judith V. M. G. Bovée","doi":"10.1002/gcc.23253","DOIUrl":"10.1002/gcc.23253","url":null,"abstract":"<p>Osteosarcoma is a primary bone tumor that exhibits a complex genomic landscape characterized by gross chromosomal abnormalities. Osteosarcoma patients often develop metastatic disease, resulting in limited therapeutic options and poor survival rates. To gain knowledge on the mechanisms underlying osteosarcoma heterogeneity and metastatic process, it is important to obtain a detailed profile of the genomic alterations that accompany osteosarcoma progression. We performed WGS on multiple tissue samples from six patients with osteosarcoma, including the treatment naïve biopsy of the primary tumor, resection of the primary tumor after neoadjuvant chemotherapy, local recurrence, and distant metastases. A comprehensive analysis of single-nucleotide variants (SNVs), structural variants, copy number alterations (CNAs), and chromothripsis events revealed the genomic heterogeneity during osteosarcoma progression. SNVs and structural variants were found to accumulate over time, contributing to an increased complexity of the genome of osteosarcoma during disease progression. Phylogenetic trees based on SNVs and structural variants reveal distinct evolutionary patterns between patients, including linear, neutral, and branched patterns. The majority of osteosarcomas showed variable copy number profiles or gained whole-genome doubling in later occurrences. Large proportions of the genome were affected by loss of heterozygosity (LOH), although these regions remain stable during progression. Additionally, chromothripsis is not confined to a single early event, as multiple other chromothripsis events may appear in later occurrences. Together, we provide a detailed analysis of the complex genome of osteosarcomas and show that five of six osteosarcoma genomes are highly dynamic and variable during progression.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 7","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23253","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633091","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}