Genomic and clinical characterization of a familial GIST kindred intolerant to imatinib.

IF 4.7 2区医学 Q1 GENETICS & HEREDITY

NPJ Genomic Medicine Pub Date : 2024-03-27 DOI:10.1038/s41525-024-00405-z

K M Ingley, M Zatzman, A M Fontebasso, W Lo, V Subasri, A Goldenberg, Y Li, S Davidson, N Kanwar, L Waldman, L Brunga, Y Babichev, E G Demicco, A Gupta, M Szybowska, S Thipphavong, D Malkin, A Villani, A Shlien, R A Gladdy, R H Kim

{"title":"Genomic and clinical characterization of a familial GIST kindred intolerant to imatinib.","authors":"K M Ingley, M Zatzman, A M Fontebasso, W Lo, V Subasri, A Goldenberg, Y Li, S Davidson, N Kanwar, L Waldman, L Brunga, Y Babichev, E G Demicco, A Gupta, M Szybowska, S Thipphavong, D Malkin, A Villani, A Shlien, R A Gladdy, R H Kim","doi":"10.1038/s41525-024-00405-z","DOIUrl":null,"url":null,"abstract":"<p><p>Familial gastrointestinal stromal tumors (GIST) are rare. We present a kindred with multiple family members affected with multifocal GIST who underwent whole genome sequencing of the germline and tumor. Affected individuals with GIST harbored a germline variant found within exon 13 of the KIT gene (c.1965T>G; p.Asn655Lys, p.N655K) and a variant in the MSR1 gene (c.877 C > T; p.Arg293*, pR293X). Multifocal GISTs in the proband and her mother were treated with preoperative imatinib, which resulted in severe intolerance. The clinical features of multifocal GIST, cutaneous mastocytosis, allergies, and gut motility disorders seen in the affected individuals may represent manifestations of the multifunctional roles of KIT in interstitial cells of Cajal or mast cells and/or may be suggestive of additional molecular pathways which can contribute to tumorigenesis.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"9 1","pages":"24"},"PeriodicalIF":4.7000,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10973472/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"NPJ Genomic Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41525-024-00405-z","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}

引用次数: 0

Abstract

Familial gastrointestinal stromal tumors (GIST) are rare. We present a kindred with multiple family members affected with multifocal GIST who underwent whole genome sequencing of the germline and tumor. Affected individuals with GIST harbored a germline variant found within exon 13 of the KIT gene (c.1965T>G; p.Asn655Lys, p.N655K) and a variant in the MSR1 gene (c.877 C > T; p.Arg293*, pR293X). Multifocal GISTs in the proband and her mother were treated with preoperative imatinib, which resulted in severe intolerance. The clinical features of multifocal GIST, cutaneous mastocytosis, allergies, and gut motility disorders seen in the affected individuals may represent manifestations of the multifunctional roles of KIT in interstitial cells of Cajal or mast cells and/or may be suggestive of additional molecular pathways which can contribute to tumorigenesis.

Abstract Image

查看原文本刊更多论文

对伊马替尼不耐受的家族性 GIST 亲属的基因组和临床特征。

家族性胃肠道间质瘤（GIST）非常罕见。我们介绍了一个多家族成员患有多灶性胃肠道间质瘤的家族，他们都接受了种系和肿瘤的全基因组测序。受影响的 GIST 患者在 KIT 基因第 13 号外显子（c.1965T>G；p.Asn655Lys, p.N655K）和 MSR1 基因（c.877 C > T；p.Arg293*, pR293X）中发现了一个种系变异。该患者及其母亲的多灶性 GIST 曾接受过术前伊马替尼治疗，但出现了严重的不耐受。患者身上出现的多灶性 GIST、皮肤肥大细胞增多症、过敏和肠道运动障碍等临床特征，可能代表了 KIT 在 Cajal 间质细胞或肥大细胞中的多功能作用，和/或可能提示了其他有助于肿瘤发生的分子途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

NPJ Genomic Medicine Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

9.40

自引率

1.90%

发文量

审稿时长

17 weeks

期刊介绍： npj Genomic Medicine is an international, peer-reviewed journal dedicated to publishing the most important scientific advances in all aspects of genomics and its application in the practice of medicine. The journal defines genomic medicine as "diagnosis, prognosis, prevention and/or treatment of disease and disorders of the mind and body, using approaches informed or enabled by knowledge of the genome and the molecules it encodes." Relevant and high-impact papers that encompass studies of individuals, families, or populations are considered for publication. An emphasis will include coupling detailed phenotype and genome sequencing information, both enabled by new technologies and informatics, to delineate the underlying aetiology of disease. Clinical recommendations and/or guidelines of how that data should be used in the clinical management of those patients in the study, and others, are also encouraged.