دورية أكاديمية
أعرض في EDS

Whole exome sequencing identifies MAP3K1, MSH2, and MLH1 as potential cancer-predisposing genes in familial early-onset colorectal cancer.

التفاصيل البيبلوغرافية
العنوان: Whole exome sequencing identifies MAP3K1, MSH2, and MLH1 as potential cancer-predisposing genes in familial early-onset colorectal cancer.
المؤلفون: Fatemi N; Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Tu SJ; Center for Precision Medicine, China Medical University Hospital, Taichung, Taiwan., Chung CC; Center for Precision Medicine, China Medical University Hospital, Taichung, Taiwan., Moghadam PK; Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Mojarad EN; Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Sadeghi A; Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Totonchi M; Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.; Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran., Aghdaei HA; Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Chang JG; Center for Precision Medicine, China Medical University Hospital, Taichung, Taiwan.; Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan.
المصدر: The Kaohsiung journal of medical sciences [Kaohsiung J Med Sci] 2023 Sep; Vol. 39 (9), pp. 896-903. Date of Electronic Publication: 2023 Jun 14.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Department of Public Health, Kaohsiung Medical University Country of Publication: China (Republic : 1949- ) NLM ID: 100960562 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2410-8650 (Electronic) Linking ISSN: 1607551X NLM ISO Abbreviation: Kaohsiung J Med Sci Subsets: MEDLINE
أسماء مطبوعة: Publication: 2019- : [Kaohsiung City, Taiwan] : Department of Public Health, Kaohsiung Medical University
Original Publication: [Kaohsiung City, Taiwan, Republic of China : Kaohsiung Medical College, 1996-
مواضيع طبية MeSH: Colorectal Neoplasms*/genetics , MAP Kinase Kinase Kinase 1*/genetics, Humans ; MutS Homolog 2 Protein/genetics ; Exome Sequencing ; Mutation/genetics ; Genetic Predisposition to Disease ; MutL Protein Homolog 1/genetics
مستخلص: The incidence of early-onset colorectal cancer (CRC), which affects people under 50, is increasing for unknown reasons. Additionally, no underlying genetic cause is found in 20%-30% of patients suspected of having familial CRC syndrome. Whole exome sequencing (WES) has generated evidence for new genes associated with CRC susceptibility, but many patients remain undiagnosed. This study applied WES in five early-onset CRC patients from three unrelated families to identify novel genetic variants that could be linked to rapid disease development. Furthermore, the candidate variants were validated using Sanger sequencing. Two heterozygote variations, c.1077-2A>G and c.199G>A, were found in the MSH2 and the MLH1 genes, respectively. Sanger sequencing analysis confirmed that these (likely) pathogenic mutations segregated in all the affected families' members. In addition, we identified a rare heterozygote variant (c.175C>T) with suspected pathogenic potential in the MAP3K1 gene; formally the variant is of uncertain significance (VUS). Our findings support the hypothesis that CRC onset may be oligogenic and molecularly heterogeneous. Larger and more robust studies are needed to understand the genetic basis of early-onset CRC development, combined with novel functional analyses and omics approaches.
(© 2023 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)
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معلومات مُعتمدة: DMR-112-233 China Medical University Hospital
فهرسة مساهمة: Keywords: colorectal cancer; early-onset; likely pathogenic; whole exome sequencing
المشرفين على المادة: EC 3.6.1.3 (MutS Homolog 2 Protein)
0 (MLH1 protein, human)
EC 3.6.1.3 (MutL Protein Homolog 1)
EC 3.6.1.3 (MSH2 protein, human)
EC 2.7.11.25 (MAP3K1 protein, human)
EC 2.7.11.25 (MAP Kinase Kinase Kinase 1)
تواريخ الأحداث: Date Created: 20230614 Date Completed: 20230913 Latest Revision: 20230913
رمز التحديث: 20240628
DOI: 10.1002/kjm2.12715
PMID: 37314251
قاعدة البيانات: MEDLINE
الوصف
تدمد:2410-8650
DOI:10.1002/kjm2.12715