NDLI: Non-truncating hMLH1 variants identified in Slovenian gastric cancer patients are not associated with Lynch Syndrome: a functional analysis report

Content Provider	Springer Nature Link
Author	Vogelsang, Matjaz Komel, Radovan
Copyright Year	2010
Abstract	Hereditary non-polyposis colorectal cancer is the most common known genetic syndrome that predisposes to various types of cancer including gastric cancer and occures mainly due to pathogenic germline mutations in DNA mismatch repair (MMR) genes, such as MLH1, MSH2 and MSH6. Impaired MMR activity can lead to microsatellite instability (MSI) in tumor tissues. Interpreting the pathogenic significance of identified mutations in MMR genes, especially missense alterations and short in-frame deletions and insertions is challenging and functional analysis is often needed to accurately assess their pathogenicities. The purpose of this study was to evaluate functional significance of MLH1 missense mutations, previously identified in unrelated Slovenian patients with MSI-positive gastric carinomas. A novel in vivo yeast-based approach and in silico predictions were used. Variant E433Q was characterized for the first time and was shown to have no effect on MLH1 protein function. Functional analysis of amino acid rearrangement K618A, with previously reported contradictory results of its pathogenicity, suggests that the variant is a neutral polymorphism. Results of our study imply that there is either germline mutation or an epigenetic inactivation of another MMR gene, which causes MSI phenotype in the referred gastric cancer cases.
Starting Page	255
Ending Page	263
Page Count	9
File Format	PDF
ISSN	13899600
Journal	Familial Cancer
Volume Number	10
Issue Number	2
e-ISSN	15737292
Language	English
Publisher	Springer Netherlands
Publisher Date	2010-12-07
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	HNPCC Gastric cancer MSI hMLH1 variants Functional analysis Yeast Cancer Research Biomedicine general Epidemiology Human Genetics
Content Type	Text
Resource Type	Article
Subject	Genetics Cancer Research Genetics (clinical) Oncology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Q48P mutation in the hMLH1 gene associated with Lynch syndrome in three Hungarian families

Missense variants in hMLH1 identified in patients from the German HNPCC consortium and functional studies

Analysis of mismatch repair gene mutations in Turkish HNPCC patients

The mechanism of mismatch repair and the functional analysis of mismatch repair defects in Lynch syndrome

Atypical identification of Lynch syndrome by immunohistochemistry and microsatellite instability analysis on jejunal adenocarcinoma

Lynch Syndrome in high risk Ashkenazi Jews in Israel

Gene variants of unknown clinical significance in Lynch syndrome. An introduction for clinicians

Mutation spectrum in HNPCC in the Israeli population

Determination of splice-site mutations in Lynch syndrome (hereditary non-polyposis colorectal cancer) patients using functional splicing assay

Non-truncating hMLH1 variants identified in Slovenian gastric cancer patients are not associated with Lynch Syndrome: a functional analysis report

Similar Documents

Q48P mutation in the hMLH1 gene associated with Lynch syndrome in three Hungarian families

Missense variants in hMLH1 identified in patients from the German HNPCC consortium and functional studies

Analysis of mismatch repair gene mutations in Turkish HNPCC patients

The mechanism of mismatch repair and the functional analysis of mismatch repair defects in Lynch syndrome

Atypical identification of Lynch syndrome by immunohistochemistry and microsatellite instability analysis on jejunal adenocarcinoma

Lynch Syndrome in high risk Ashkenazi Jews in Israel

Gene variants of unknown clinical significance in Lynch syndrome. An introduction for clinicians

Mutation spectrum in HNPCC in the Israeli population

Determination of splice-site mutations in Lynch syndrome (hereditary non-polyposis colorectal cancer) patients using functional splicing assay

Non-truncating hMLH1 variants identified in Slovenian gastric cancer patients are not associated with Lynch Syndrome: a functional analysis report