Genes, Chromosomes & Cancer最新文献_第10页

Novel ATG7::RAF1 gene fusion in malignant glomus tumor 新型ATG7:：RAF1基因融合治疗恶性肾小球肿瘤。

IF 3.7 2区医学

Genes, Chromosomes & Cancer Pub Date : 2023-09-19 DOI: 10.1002/gcc.23202

Saba Shafi, Dan Jones, O. Hans Iwenofu, Swati Satturwar

{"title":"Novel ATG7::RAF1 gene fusion in malignant glomus tumor","authors":"Saba Shafi, Dan Jones, O. Hans Iwenofu, Swati Satturwar","doi":"10.1002/gcc.23202","DOIUrl":"10.1002/gcc.23202","url":null,"abstract":"Glomus tumors are classified as members of the perivascular myoid family of tumors. Nearly half of these show NOTCH-gene fusions and a smaller subset has BRAF V600E mutations. Here, we report a novel ATG7::RAF1 fusion in malignant glomus tumor occurring in a 40-year-old female which has not been reported in the malignant glomus tumor before. A 40-year-old female presented with a persistent lateral heel pain and an increase in the size of a mass along the lateral ankle for nearly 10 years. Resected specimen showed a well circumscribed lesion composed of spindled and epithelioid cells with moderate nuclear atypia and mitotic figures (7/10 high-power fields) including atypical forms without any necrosis, lymphovascular, or perineural invasion. The tumor was positive for smooth muscle actin, smooth muscle myosin heavy chain, H-caldesmon, collagen type IV, and discovered on gastronintestinal stromal tumors-1 but negative for AE1/3, desmin, S-100, CD34, and CD117. RNA sequencing showed presence of ATG7-RAF1 fusion. This fusion has not been reported in the malignant glomus tumor before. Future studies on larger cohorts are needed to ascertain the biological significance of these tumors with novel gene fusions.","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41132087","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}

引用次数: 0

Novel NCOA2/3-rearranged low-grade fibroblastic spindle cell tumors: A report of five cases 新型NCOA2/3重排低级别成纤维细胞梭形细胞肿瘤：5例报告。

IF 3.7 2区医学

Genes, Chromosomes & Cancer Pub Date : 2023-09-19 DOI: 10.1002/gcc.23203

Ahmed Bakhshwin, Susan M. Armstrong, Lauren A. Duckworth, Robert Stoehr, Eiichi Konishi, Brian P. Rubin, Karen J. Fritchie, Brendan C. Dickson, Abbas Agaimy, Josephine K. Dermawan

{"title":"Novel NCOA2/3-rearranged low-grade fibroblastic spindle cell tumors: A report of five cases","authors":"Ahmed Bakhshwin, Susan M. Armstrong, Lauren A. Duckworth, Robert Stoehr, Eiichi Konishi, Brian P. Rubin, Karen J. Fritchie, Brendan C. Dickson, Abbas Agaimy, Josephine K. Dermawan","doi":"10.1002/gcc.23203","DOIUrl":"10.1002/gcc.23203","url":null,"abstract":"Spindle cell mesenchymal neoplasms are a diverse and often challenging diagnostic group. While morphological impression is sufficient for some diagnoses, increasingly immunohistochemical and even molecular data is required to render an accurate diagnosis, which can lead to the characterization of new entities. We describe five cases of novel mesenchymal neoplasms with rearrangements in the NCOA2 and NCOA3 genes partnered with either CTCF or CRTC1. Three tumors occurred in the head and neck (palate, auditory canal), while the other two were in visceral organs (lung, urinary bladder). All cases occurred in adults (range 33–86) with a median age of 42 and fairly even sex distribution = (male-to-female = 3:2). Morphologically, they had similar features consisting of monotonous, bland spindle to ovoid cells with fascicular and reticular arrangements in a myxohyaline to collagenous stroma. However, immunophenotypically they had essentially a null phenotype, with only two tumors staining partially for CD34 and smooth muscle actin. Targeted RNA sequencing detected in-frame CTCF::NCOA2 (one case), CRTC1::NCOA2 (two cases), and CTCF::NCOA3 (two cases) fusions. Treatment was surgical resection in all cases. Local recurrence and/or distant metastases were not observed in any case (median follow-up, 7.5 months; range, 2–19 months). Given their morphologic, immunohistochemical, and molecular similarities, we believe that these cases may represent an emerging family of low-grade NCOA2/3-rearranged fibroblastic spindle cell neoplasms.","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23203","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41149249","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}

引用次数: 0

DICER1-mutated rhabdomyosarcoma of the ovary with teratoid features DICER1突变卵巢横纹肌肉瘤伴畸胎瘤特征。

IF 3.7 2区医学

Genes, Chromosomes & Cancer Pub Date : 2023-09-14 DOI: 10.1002/gcc.23201

Vincent Lethongsavarn, Pierre Vieille, Jeanos Kikweta Makhama, Rihab Azmani, Webert Lafrance, Pierre Khneisser, Nathalene Truffaut, Melissa Alame, Catherine Genestie, Nathalie Gaspar, Abdoulaye Diedhiou, Sabrina Croce, François Le Loarer

{"title":"DICER1-mutated rhabdomyosarcoma of the ovary with teratoid features","authors":"Vincent Lethongsavarn, Pierre Vieille, Jeanos Kikweta Makhama, Rihab Azmani, Webert Lafrance, Pierre Khneisser, Nathalene Truffaut, Melissa Alame, Catherine Genestie, Nathalie Gaspar, Abdoulaye Diedhiou, Sabrina Croce, François Le Loarer","doi":"10.1002/gcc.23201","DOIUrl":"10.1002/gcc.23201","url":null,"abstract":"DICER1-mutated rhabdomyosarcoma is a rare, emerging entity with a predilection for the gynecologic and genitourinary tracts. We report here a case of DICER1-mutated rhabdomyosarcoma of the ovary in a 14 years old girl which displayed interspersed mature teratoid glands, neuroectodermal rosettes and immature blastematous-like tubes. Morphologically the sarcomatous component predominated, corresponding to a high grade spindle cell rhabdomyosarcoma with botryoid features. Islets of cartilage were present. The sarcomatous proliferation encased the teratoid glands, forming cambium layer-like arrangements. The sarcoma cells were Myogenin and MYOD1 positive, the neuroectodermal rosettes expressed SALL4 along with cytokeratins and EMA and were negative for Inhibin; immature blastematous-like tubes were negative for SALL4 and Inhibin. Whole RNA- and targeted DNA-sequencing revealed two DICER1 mutations in exon 26: c.5113G>A: p.(Glu1705Lys) and exon 12: c.1642C>T: p.(Gln548X). The sarcomatous component harbored a complex genetic profile while the teratoid component was diploid, none of the above displayed abnormality of 12p. DICER1-mutated sarcomas display pathological features similar to embryonal rhabdomyosarcomas, botryoid type. They also display heterogeneous features combining cartilage foci, teratoid mature glands, immature blastematous-like tubes and/or neuroectodermal components. Molecular testing remains necessary to confirm the diagnosis. Further studies need to clarify the nosology of DICER1-mutated sarcomas and devise specific therapeutic strategies.","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"62 12","pages":"746-754"},"PeriodicalIF":3.7,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23201","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10230512","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}

引用次数: 0

Complementary value of molecular analysis to expert review in refining classification of uncommon soft tissue tumors 分子分析与专家审查在完善不常见软组织肿瘤分类方面的互补价值。

IF 3.7 2区医学

Genes, Chromosomes & Cancer Pub Date : 2023-09-13 DOI: 10.1002/gcc.23196

Albert J. H. Suurmeijer, Brendan C. Dickson, Cristina R. Antonescu

{"title":"Complementary value of molecular analysis to expert review in refining classification of uncommon soft tissue tumors","authors":"Albert J. H. Suurmeijer, Brendan C. Dickson, Cristina R. Antonescu","doi":"10.1002/gcc.23196","DOIUrl":"10.1002/gcc.23196","url":null,"abstract":"The classification of many soft tissue tumors remains subjective due their rarity, significant overlap in microscopic features and often a non-specific immunohistochemical (IHC) profile. The application of molecular genetic tools, which leverage the underlying molecular pathogenesis of these neoplasms, have considerably improved the diagnostic abilities of pathologists and refined classification based on objective molecular markers. In this study, we describe the results of an international collaboration conducted over a 3-year period, assessing the added diagnostic value of applying molecular genetics to sarcoma expert pathologic review in a selected series of 84 uncommon, mostly unclassifiable mesenchymal tumors, 74 of which originated in soft tissues and 10 in bone. The case mix (71% historical, 29% contemporary) included mostly unusual and challenging soft tissue tumors, which remained unclassified even with the benefit of expert review and routine ancillary methods, including broad IHC panels and a limited number of commercially available fluorescence in situ hybridization (FISH) probes. All cases were further tested by FISH using a wide range of custom bacterial artificial chromosome probes covering most of known fusions in sarcomas, whereas targeted RNA sequencing was performed in 13 cases negative by FISH, for potential discovery of novel fusion genes. Tumor-defining molecular alterations were found in 48/84 tumors (57%). In 27 (32%) cases the tumor diagnosis was refined or revised by the additional molecular work-up, including five cases (6%), in which the updated diagnosis had clinical implications. Sarcoma classification is rapidly evolving due to an increased molecular characterization of these neoplasms, so unsurprisingly 17% of the tumors in this series harbored abnormalities only very recently described as defining novel molecularly defined soft tissue tumor subsets.","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10278683","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}

引用次数: 0

A novel HMGA2::KITLG fusion in a dedifferentiated liposarcoma with amplification of MDM2 and HMGA2 一种新型 HMGA2::KITLG融合型脂肪肉瘤伴有MDM2和HMGA2扩增。

IF 3.7 2区医学

Genes, Chromosomes & Cancer Pub Date : 2023-09-12 DOI: 10.1002/gcc.23200

Shishan Zhou, Changliang Zhang, Zhipeng Zhang, Yongbin Hu, Lina Zhao, Wentao Hu, Si Chen, Bin Li, Sheng Xiao

{"title":"A novel HMGA2::KITLG fusion in a dedifferentiated liposarcoma with amplification of MDM2 and HMGA2","authors":"Shishan Zhou, Changliang Zhang, Zhipeng Zhang, Yongbin Hu, Lina Zhao, Wentao Hu, Si Chen, Bin Li, Sheng Xiao","doi":"10.1002/gcc.23200","DOIUrl":"10.1002/gcc.23200","url":null,"abstract":"High-mobility group AT-hook 2 (HMGA2) is rearranged in various types of mesenchymal tumors, particularly lipomas. HMGA2 is also co-amplified with mouse double minute 2 (MDM2) in well-differentiated liposarcoma/dedifferentiated liposarcoma (WDLPS/DDLPS). We report a case of relapsed DDLPS with a novel in-frame fusion between HMGA2 and KITLG, which encodes the ligand for KIT kinase, a critical protein involved in gametogenesis, hematopoiesis, and melanogenesis. The HMGA2 breakpoint is in intron 3, a commonly observed location for HMGA2 rearrangements, while the KITLG breakpoint is in intron 2, leading to a fusion protein that contains almost the entire coding sequence of KITLG. By immunohistochemical staining, tumor cells expressed KIT and showed phosphorylated MAPK, a major KIT downstream target. We suggest an oncogenic mechanism that involves the overexpression of KITLG caused by its rearrangement with HMGA2, leading to the constitutive activation of KIT kinase. While MDM2 amplification was observed in both the primary tumor and the relapsed tumor, the HMGA2::KITLG was only present in the relapsed tumor, indicating the role of HMGA2::KITLG in disease progression.","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10564670","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}

引用次数: 0

Frequency of genetic alterations differs in advanced breast cancer between metastatic sites 晚期乳腺癌不同转移部位的基因改变频率不同。

IF 3.7 2区医学

Genes, Chromosomes & Cancer Pub Date : 2023-09-06 DOI: 10.1002/gcc.23199

Isabel Grote, Alexandra Poppe, Ulrich Lehmann, Matthias Christgen, Hans Kreipe, Stephan Bartels

{"title":"Frequency of genetic alterations differs in advanced breast cancer between metastatic sites","authors":"Isabel Grote, Alexandra Poppe, Ulrich Lehmann, Matthias Christgen, Hans Kreipe, Stephan Bartels","doi":"10.1002/gcc.23199","DOIUrl":"10.1002/gcc.23199","url":null,"abstract":"About 20%–30% of breast cancer (BC) patients will develop distant metastases, preferentially in bones, liver, lung, and brain. BCs with different intrinsic subtypes prefer different sites for metastasis. These subtypes vary in the abundance of genetic alterations which may influence the localization of metastases. Currently, information about the relation between metastatic site and mutational profile of BC is limited. In this study, n = 521 BC metastases of the most frequently affected sites (bone, brain, liver, and lung) were investigated for the frequency of AKT1, ERBB2, ESR1, PIK3CA, and TP53 mutations via NGS and pyrosequencing. Somatic mutations were present in 64% cases. PIK3CA and TP53 were the most frequently mutated genes under study. We provide an analysis of the mutational profile of BCs and the affected metastatic site. Genetic alterations differed significantly depending on the organ site affected by metastases. TP53 mutations were mostly observed in brain metastases (51.0%), metastases outside of the brain revealed a much lower proportion of TP53 mutated samples. PIK3CA mutations are frequent in liver (40.6%), lung (36.8%), and bone metastases (35.7%), whereas less common in brain metastases (18.4%). The highest percentage of ESR1 mutations was observed in liver and lung metastases (about 30% each), whereas metastatic lesions in the brain showed significantly less ESR1 mutations, only in 2.0% of the cases. In summary, we found significant differences of mutational status in mBC depending on the affected organ and intrinsic subtype. Organotropism of metastatic cancer spread may be influenced by the mutational profile of individual BCs.","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23199","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10160739","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}

引用次数: 0

Untying the Gordian knot of composite hemangioendothelioma: Discovery of novel fusions 解开复合型血管内皮瘤的死结：发现新型融合体

IF 3.7 2区医学

Genes, Chromosomes & Cancer Pub Date : 2023-09-02 DOI: 10.1002/gcc.23198

Konstantinos Linos, Josephine K. Dermawan, Melissa Pulitzer, Meera Hameed, Narasimhan P. Agaram, Abbas Agaimy, Cristina R. Antonescu

{"title":"Untying the Gordian knot of composite hemangioendothelioma: Discovery of novel fusions","authors":"Konstantinos Linos, Josephine K. Dermawan, Melissa Pulitzer, Meera Hameed, Narasimhan P. Agaram, Abbas Agaimy, Cristina R. Antonescu","doi":"10.1002/gcc.23198","DOIUrl":"10.1002/gcc.23198","url":null,"abstract":"Composite hemangioendothelioma is a rare, locally aggressive, and rarely metastasizing vascular neoplasm which affects both children and adults. Recently, a number of gene fusions including YAP1::MAML2, PTBP1::MAML2, and EPC1::PHC2 have been detected in a small subset of cases with or without neuroendocrine expression. Herein, we present four additional cases with novel in-frame fusions. The cohort comprises two females and two males with a wide age range at diagnosis (24–80 years). Two tumors were deep involving the right brachial plexus and mediastinum, while the remaining were superficial (right plantar foot and abdominal wall). The size ranged from 1.5 to 4.8 cm in greatest dimension. Morphologically, all tumors had an admixture of at least two architectural patterns including retiform hemangioendothelioma, hemangioma, epithelioid hemangioendothelioma, or angiosarcoma. The tumors were positive for endothelial markers CD31 (3/3), ERG (4/4), and D2-40 (1/4, focal), while SMA was expressed in 2/3 highlighting the surrounding pericytes. Synaptophysin showed immunoreactivity in 2/3 cases. One patient had a local recurrence after 40 months, while two patients had no evidence of disease 4 months post-resection. Targeted RNA sequencing detected novel in-frame fusions in each of the cases: HSPG2::FGFR1, YAP1::FOXR1, ACTB::MAML2, and ARID1B::MAML2. The two cases with neuroendocrine expression occurred as superficial lesions and harbored YAP1::FOXR1 and ARID1B::MAML2 fusions. Our study expands on the molecular spectrum of this enigmatic tumor, further enhancing our current understanding of the disease.","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10511544","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}

引用次数: 0

Expanding the spectrum of tyrosine kinase fusions in calcified chondroid mesenchymal neoplasms: Identification of a novel PDGFRA::USP8 gene fusion 扩大钙化软骨间充质肿瘤中酪氨酸激酶融合的范围：鉴定新型PDGFRA::USP8基因融合体。

IF 3.7 2区医学

Genes, Chromosomes & Cancer Pub Date : 2023-08-29 DOI: 10.1002/gcc.23197

Yael Fisher, Maribel D. Lacambra, Shahd S. Almohsen, Chit Chow, Jason L. Hornick, Ka-Fai To, Brendan C. Dickson

{"title":"Expanding the spectrum of tyrosine kinase fusions in calcified chondroid mesenchymal neoplasms: Identification of a novel PDGFRA::USP8 gene fusion","authors":"Yael Fisher, Maribel D. Lacambra, Shahd S. Almohsen, Chit Chow, Jason L. Hornick, Ka-Fai To, Brendan C. Dickson","doi":"10.1002/gcc.23197","DOIUrl":"10.1002/gcc.23197","url":null,"abstract":"Calcified chondroid mesenchymal neoplasms represent a distinct, and recently recognized, spectrum of tumors. To date most cases have been reported to be characterized by FN1 gene fusions involving multiple potential tyrosine kinase partners. Following incidental identification of a tumor morphologically corresponding to calcified chondroid mesenchymal neoplasm, but with a PDGFRA::USP8 gene fusion, we undertook a retrospective review to identify and characterize additional such cases. A total of four tumors were identified. Each was multilobulated and composed of polygonal-epithelioid-stellate cells with a background of chondroid matrix containing distinctive patterns of calcification. Targeted RNA sequencing revealed an identical PDGFRA (exon 22)::USP8 (exon 5) gene fusion in each case. Subsequent immunohistochemical staining confirmed the presence of PDGFRα overexpression. In summary, we report a series of four tumors within the morphologic spectrum of calcified chondroid mesenchymal neoplasms. In contrast to prior reports, these tumors harbored a novel PDGFRA::USP8 gene fusion, rather than FN1 rearrangement. Our findings expand the molecular diversity of these neoplasms, and suggest they are united through activation of protein kinases.","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10485366","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}

引用次数: 0

Constitutional balanced translocations involving SMARCB1: A rare cause of rhabdoid tumor predisposition syndrome 涉及 SMARCB1 的体质平衡易位：横纹肌瘤易感综合征的罕见病因

IF 3.7 2区医学

Genes, Chromosomes & Cancer Pub Date : 2023-08-07 DOI: 10.1002/gcc.23195

Patrick R. Blackburn, Rose B. McGee, Roya Mostafavi, Andrew J. Carroll, Fady M. Mikhail, Gregory T. Armstrong, Larissa V. Furtado, Jason Chiang, David A. Wheeler, Steven S. Carey, Kim E. Nichols, Santhosh A. Upadhyaya

{"title":"Constitutional balanced translocations involving SMARCB1: A rare cause of rhabdoid tumor predisposition syndrome","authors":"Patrick R. Blackburn, Rose B. McGee, Roya Mostafavi, Andrew J. Carroll, Fady M. Mikhail, Gregory T. Armstrong, Larissa V. Furtado, Jason Chiang, David A. Wheeler, Steven S. Carey, Kim E. Nichols, Santhosh A. Upadhyaya","doi":"10.1002/gcc.23195","DOIUrl":"10.1002/gcc.23195","url":null,"abstract":"Rhabdoid Tumor Predisposition Syndrome 1 (RTPS1) confers an increased risk of developing rhabdoid tumors and is caused by germline mutations in SMARCB1. RTPS1 should be evaluated in all individuals with rhabdoid tumor and is more likely in those with a young age at presentation (occasionally congenital presentation), multiple primary tumors, or a family history of rhabdoid tumor or RTPS1. Proband genetic testing is the standard method for diagnosing RTPS1. Most known RTPS1-related SMARCB1 gene mutations are copy number variants (CNVs) or single nucleotide variants/indels, but structural variant analysis (SVA) is not usually included in the molecular evaluation. Here, we report two children with RTPS1 presenting with atypical teratoid/rhabdoid tumor (ATRT) who had constitutional testing showing balanced chromosome translocations involving SMARCB1. Patient 1 is a 23-year-old female diagnosed with pineal region ATRT at 7 months who was found to have a de novo, constitutional t(16;22)(p13.3;q11.2). Patient 2 is a 24-month-old male diagnosed with a posterior fossa ATRT at 14 months, with subsequent testing showing a constitutional t(5;22)(q14.1;q11.23). These structural rearrangements have not been previously reported in RTPS1. While rare, these cases suggest that structural variants should be considered in the evaluation of children with rhabdoid tumors to provide more accurate genetic counseling on the risks of developing tumors, the need for surveillance, and the risks of passing the disorder on to future children. Further research is needed to understand the prevalence, clinical features, and tumor risks associated with RTPS1-related constitutional balanced translocations.","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10000637","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}

引用次数: 0

PMS2 or PMS2CL? Characterization of variants detected in the 3′ of the PMS2 gene PMS2 还是 PMS2CL？PMS2 基因 3' 端检测到的变异的特征。

IF 3.7 2区医学

Genes, Chromosomes & Cancer Pub Date : 2023-08-03 DOI: 10.1002/gcc.23193

Ahmed Bouras, Cedrick Lefol, Eric Ruano, Chloé Grand-Masson, Qing Wang

{"title":"PMS2 or PMS2CL? Characterization of variants detected in the 3′ of the PMS2 gene","authors":"Ahmed Bouras, Cedrick Lefol, Eric Ruano, Chloé Grand-Masson, Qing Wang","doi":"10.1002/gcc.23193","DOIUrl":"10.1002/gcc.23193","url":null,"abstract":"PMS2 germline pathogenic variants are one of the major causes for Lynch syndrome and constitutional mismatch repair deficiencies. Variant identification in the 3′ region of this gene is complicated by the presence of the pseudogene PMS2CL which shares a high sequence homology with PMS2. Consequently, short-fragment screening strategies (NGS, Sanger) may fail to discriminate variant's gene localization. Using a comprehensive analysis strategy, we assessed 42 NGS-detected variants in 76 patients and found 32 localized on PMS2 while 6 on PMS2CL. Interestingly, four variants were detected in either of them in different patients. Clinical phenotype was well correlated to genotype, making it very helpful in variant assessment. Our findings emphasize the necessity of more specific complementary analyses to confirm the gene origin of each variant detected in different individuals in order to avoid variant misinterpretation. In addition, we characterized two PMS2 genomic alterations involving Alu-mediated tandem duplication and gene conversion. Those mechanisms seemed to be particularly favored in PMS2 which contribute to frequent genomic rearrangements in the 3′ region of the gene.","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23193","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9927044","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}

引用次数: 0