دورية أكاديمية
MLH1 Promotor Hypermethylation in Colorectal and Endometrial Carcinomas from Patients with Lynch Syndrome.
| العنوان: | MLH1 Promotor Hypermethylation in Colorectal and Endometrial Carcinomas from Patients with Lynch Syndrome. |
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| المؤلفون: | Helderman NC; Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands., Andini KD; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., van Leerdam ME; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands; Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands., van Hest LP; Department of Human Genetics, Amsterdam University Medical Center, Vrije Universiteit Amsterdam and University of Amsterdam, Amsterdam, the Netherlands., Hoekman DR; Department of Human Genetics, Amsterdam University Medical Center, Vrije Universiteit Amsterdam and University of Amsterdam, Amsterdam, the Netherlands., Ahadova A; Department of Applied Tumor Biology, Heidelberg University Hospital, Clinical Cooperation Unit Applied Tumor Biology, German Cancer Research Centre, Heidelberg, Germany., Bajwa-Ten Broeke SW; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., Bosse T; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands., van der Logt EMJ; Department of Molecular Diagnostics, Pathology Friesland, Leeuwarden, the Netherlands., Imhann F; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., Kloor M; Department of Applied Tumor Biology, Heidelberg University Hospital, Clinical Cooperation Unit Applied Tumor Biology, German Cancer Research Centre, Heidelberg, Germany., Langers AMJ; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands., Smit VTHBM; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands., Terlouw D; Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands., van Wezel T; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands., Morreau H; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands., Nielsen M; Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: m.nielsen@lumc.nl. |
| المصدر: | The Journal of molecular diagnostics : JMD [J Mol Diagn] 2024 Feb; Vol. 26 (2), pp. 106-114. Date of Electronic Publication: 2023 Dec 05. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 100893612 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1943-7811 (Electronic) Linking ISSN: 15251578 NLM ISO Abbreviation: J Mol Diagn Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2011- : New York : Elsevier Original Publication: Bethesda, MD : American Society for Investigative Pathology and the Association for Molecular Pathology, 1999- |
| مواضيع طبية MeSH: | Colorectal Neoplasms, Hereditary Nonpolyposis*/diagnosis , Colorectal Neoplasms, Hereditary Nonpolyposis*/genetics , Endometrial Neoplasms*/diagnosis , Endometrial Neoplasms*/genetics , Endometrial Neoplasms*/pathology, Female ; Humans ; Middle Aged ; Aged ; MutL Protein Homolog 1/genetics ; MutL Protein Homolog 1/metabolism ; Genetic Testing ; Promoter Regions, Genetic ; DNA Mismatch Repair/genetics ; Mismatch Repair Endonuclease PMS2/genetics ; Mismatch Repair Endonuclease PMS2/metabolism ; Germ-Line Mutation |
| مستخلص: | Screening for Lynch syndrome (LS) in colorectal cancer (CRC) and endometrial cancer patients generally involves immunohistochemical staining of the mismatch repair (MMR) proteins. In case of MLH1 protein loss, MLH1 promotor hypermethylation (MLH1-PM) testing is performed to indirectly distinguish the constitutional MLH1 variants from somatic epimutations. Recently, multiple studies have reported that MLH1-PM and pathogenic constitutional MMR variants are not mutually exclusive. This study describes 6 new and 86 previously reported MLH1-PM CRCs or endometrial cancers in LS patients. Of these, methylation of the MLH1 gene promotor C region was reported in 30 MLH1, 6 MSH2, 6 MSH6, and 3 PMS2 variant carriers at a median age at diagnosis of 48.5 years [interquartile range (IQR), 39-56.75 years], 39 years (IQR, 29-51 years), 58 years (IQR, 53.5-67 years), and 68 years (IQR, 65.6-68.5 years), respectively. For 31 MLH1-PM CRCs in LS patients from the literature, only the B region of the MLH1 gene promotor was tested, whereas for 13 cases in the literature the tested region was not specified. Collectively, these data indicate that a diagnosis of LS should not be excluded when MLH1-PM is detected. Clinicians should carefully consider whether follow-up genetic MMR gene testing should be offered, with age <60 to 70 years and/or a positive family history among other factors being suggestive for a potential constitutional MMR gene defect. Competing Interests: Disclosure Statement None declared. (Copyright © 2024 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.) |
| المشرفين على المادة: | EC 3.6.1.3 (MutL Protein Homolog 1) EC 3.6.1.3 (Mismatch Repair Endonuclease PMS2) 0 (MLH1 protein, human) |
| تواريخ الأحداث: | Date Created: 20231207 Date Completed: 20240126 Latest Revision: 20240607 |
| رمز التحديث: | 20240607 |
| DOI: | 10.1016/j.jmoldx.2023.10.005 |
| PMID: | 38061582 |
| قاعدة البيانات: | MEDLINE |
Full Text via ClinicalKey 
Full Text Finder | تدمد: | 1943-7811 |
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| DOI: | 10.1016/j.jmoldx.2023.10.005 |