Germline mutations of hMLH1 and hMSH2 genes in patients with suspected hereditary nonpolyposis colorectal cancer and sporadic early-onset colorectal cancer

1998 ◽  
Vol 41 (4) ◽  
pp. 434-440 ◽  
Author(s):  
Ying Yuan ◽  
Hye-Jung Han ◽  
Shu Zheng ◽  
Jae-Gahb Park
Keyword(s):  
Colorectal Cancer ◽  
Early Onset ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Germline Mutations ◽  
Hereditary Nonpolyposis ◽  
Early Onset Colorectal Cancer

Hereditary nonpolyposis colorectal cancer: Identification of novel germline mutations in two kindreds not fulfilling the Amsterdam criteria

1998 ◽  
Vol 12 (6) ◽  
pp. 433-433 ◽  
Author(s):  
Barbara Quaresima ◽  
Cristina Grandinetti ◽  
Francesco Baudi ◽  
PierFrancesco Tassone ◽  
Vito Barbieri ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Germline Mutations ◽  
Amsterdam Criteria ◽  
Hereditary Nonpolyposis

Molecular Screening for Hereditary Nonpolyposis Colorectal Cancer: A Prospective, Population-Based Study

2001 ◽  
Vol 19 (19) ◽  
pp. 3944-3950 ◽  
Author(s):  
Antonio Percesepe ◽  
Francesca Borghi ◽  
Mirco Menigatti ◽  
Lorena Losi ◽  
Moira Foroni ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Family History ◽  
Germline Mutation ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Germline Mutations ◽  
Screening Programs ◽  
High Incidence ◽  
Hereditary Nonpolyposis ◽  
Incident Cases ◽  
High Incidence Area

PURPOSE: Germline mutations in mismatch repair genes predispose to hereditary nonpolyposis colorectal cancer (HNPCC). To address effective screening programs, the true incidence of the disease must be known. Previous clinical investigations reported estimates ranging between 0.5% and 13% of all the colorectal cancer (CRC) cases, whereas biomolecular studies in Finland found an incidence of 2% to 2.7% of mutation carriers for the disease. The aim of the present report is to establish the frequency of the disease in a high-incidence area for colon cancer. PATIENTS AND METHODS: Through the data of the local CRC registry, we prospectively collected all cases of CRC from January 1, 1996, through December 31, 1997 (N = 391). Three hundred thirty-six CRC cases (85.9% of the incident cases) were screened for microsatellite instability (MSI) with six to 12 mono- and dinucleotide markers. MSI cases were subjected to MSH2 and MLH1 germline mutation analysis and immunohistochemistry; the methylation of the promoter region was studied for MLH1. RESULTS: Twenty-eight cases (8.3% of the total) showed MSI. MSI cases differed significantly from microsatellite-stable (MSS) cases for their proximal location (P < .01), high mucinous component (P < .01), and poor differentiation (P = .002). Of MSI cases studied (n = 12), only one with a family history compatible with HNPCC had a germline mutation (in MSH2). Five other patients with a family history of HNPCC (two with MSI and three with MSS tumors) did not show germline mutations. CONCLUSION: We conclude that the incidence of molecularly confirmed HNPCC (one [0.3%] of 336) in a high-incidence area for CRC is lower than in previous biomolecular and clinical estimates.

scholarly journals Identification of Germline Mutations in Hereditary Nonpolyposis Colorectal Cancer Using Base Excision Sequence Scanning Analysis

1999 ◽  
Vol 45 (9) ◽  
pp. 1564-1567 ◽  
Author(s):  
Angela Brieger ◽  
Jörg Trojan ◽  
Jochen Raedle ◽  
W Kurt Roth ◽  
Stefan Zeuzem
Keyword(s):  
Colorectal Cancer ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Germline Mutations ◽  
Hereditary Nonpolyposis ◽  
Base Excision

Enhanced Detection of Deleterious and Other Germline Mutations of hMSH2 and hMLH1 in Japanese Hereditary Nonpolyposis Colorectal Cancer Kindreds

2000 ◽  
Vol 271 (1) ◽  
pp. 120-129 ◽  
Author(s):  
Sachio Nomura ◽  
Kokichi Sugano ◽  
Hidefumi Kashiwabara ◽  
Takahiro Taniguchi ◽  
Noriko Fukayama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Germline Mutations ◽  
Hereditary Nonpolyposis

A de novo deletional germline mutation in the MLH1 gene resulting in early onset colorectal cancer in a woman with a negative family history: A case report

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21067-21067
Author(s):  
D. Zakalik ◽  
N. S. Goldstein ◽  
W. L. Ducaine
Keyword(s):  
Colorectal Cancer ◽  
Family History ◽  
Early Onset ◽  
De Novo ◽  
Germline Mutations ◽  
De Novo Mutations ◽  
Mlh1 Gene ◽  
Negative Family History ◽  
Mmr Genes ◽  
Early Onset Colorectal Cancer

21067 Background: Hereditary non-polyposis colorectal cancer (HNPCC) is a genetic disorder that results in an increased risk of early onset colorectal cancer (CRC). HNPCC is caused by germline mutations in DNA mismatch repair (MMR) genes, including MLH1 and MSH2, and is transmitted in an autosomal dominant manner. De novo germline mutations in MMR genes are exceedingly rare. We now describe a case of a de novo germline mutation in MLH1 associated with early onset CRC in a young woman with a negative family history. Methods: We present a case of a 31-year-old Caucasian female who presented with abdominal pain. Colonoscopy revealed a moderately differentiated adenocarcinoma with focal mucin production involving the sigmoid colon, with a final staging of T4N0M0. Genetic testing was offered because of her young age at diagnosis, having fulfilled the Bethesda guidelines. Microsatellite instability (MSI) testing using a panel of six microsatellite loci was performed on the tumor sample from the affected patient. Immunohistochemistry (IHC) testing for MLH1 and MSH2 was performed. Following counseling and with informed consent, DNA was isolated and sequenced using bi-directional PCR of the MLH1 gene. All exons of MLH1 and MSH2 were analyzed by standard Southern blot methods. Paternity was established using eight genetic loci. Results: The patient's tumor revealed high MSI and complete absence of MLH1 immunoreactivity. MSH2 IHC staining was normal. A large deletional mutation involving exons 5–12 of MLH1 was identified by Southern blot analysis. The patient's parents and siblings were tested and found to have wild type MLH1. Paternity was confirmed with greater than 99.9% certainty. Conclusions: De novo mutations in MMR genes are a rare cause of HNPCC. We report the first case of a large de novo deletion in the MLH1 gene accounting for early onset CRC. Such de novo mutations, albeit rare, must be considered in patients who present with early onset CRC and a negative family history. These results support the use of the Bethesda guidelines to identify individuals who may carry mutations in the MMR genes. No significant financial relationships to disclose.

Germline mutations of EXO1 gene in patients with hereditary nonpolyposis colorectal cancer (HNPCC) and atypical HNPCC forms

2001 ◽  
Vol 120 (7) ◽  
pp. 1580-1587 ◽  
Author(s):  
Ying Wu ◽  
Rob G.J. Mensink ◽  
Edwin Verlind ◽  
Rolf H. Sijmons ◽  
Charles H.C.M. Buys ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Germline Mutations ◽  
Hereditary Nonpolyposis

Prevalence of germline mutations in the spindle assembly checkpoint gene BUB1B in individuals with early-onset colorectal cancer

2016 ◽  
Vol 55 (11) ◽  
pp. 855-863 ◽  
Author(s):  
Marc-Manuel Hahn ◽  
Lilian Vreede ◽  
Sonja A. S. A Bemelmans ◽  
Erica van der Looij ◽  
Ad Geurts van Kessel ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Onset ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Germline Mutations ◽  
Checkpoint Gene ◽  
Early Onset Colorectal Cancer

Molecular Studies in Hereditary Nonpolyposis Colorectal Cancer: Microsatellite Instability and Germline Mutations

2015 ◽  
pp. 67-73
Author(s):  
Lutz Buschhausen ◽  
Martin Wehner ◽  
Christof Lamberti ◽  
Waltraut Friedl ◽  
Reiner Caspari ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Germline Mutations ◽  
Hereditary Nonpolyposis ◽  
Molecular Studies

Molecular Analysis of Familial Endometrial Carcinoma: A Manifestation of Hereditary Nonpolyposis Colorectal Cancer or a Separate Syndrome?

2005 ◽  
Vol 23 (21) ◽  
pp. 4609-4616 ◽  
Author(s):  
Miina Ollikainen ◽  
Wael M. Abdel-Rahman ◽  
Anu-Liisa Moisio ◽  
Annette Lindroos ◽  
Reetta Kariola ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Endometrial Carcinoma ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Germline Mutations ◽  
Unknown Etiology ◽  
Cancer Syndrome ◽  
Site Specific ◽  
Mmr Genes ◽  
Hereditary Nonpolyposis ◽  
Mlh1 Protein

Purpose Familial clustering of endometrial carcinoma (EC) may occur as part of hereditary nonpolyposis colorectal cancer (HNPCC), a multiorgan cancer syndrome with mismatch repair (MMR) deficiency. Clustering of EC alone, termed as familial site-specific EC, may constitute a separate entity. Because its genetic basis is unknown, our purpose was to characterize such families molecularly. Materials and Methods Twenty-three families with site-specific EC were identified among 519 consecutive patients diagnosed with EC during 1986 to 1997. Tumor tissues were examined for MMR protein expression by immunohistochemical (IHC) analysis, and MMR genes pinpointed by IHC changes were screened for germline mutations by exon-by-exon sequencing, multiplex ligation-dependent probe amplification, and direct tests for mutations common in the population. Results Among 33 ECs from 23 families, MLH1 protein was lost in seven tumors (21%), MSH2 together with MSH6 was lost in four tumors (12%), and MSH6 alone was lost in five tumors (15%). A truncating germline mutation in MSH6 (3261insC) was identified in one family and a likely pathogenic missense mutation in MSH2 (D603N) was identified in another family. Among the original 519 patients, nine (all with colon cancer in the family) were diagnosed with HNPCC at the outset—six with MLH1 and three with MSH2 mutations. Conclusion Our study gives a minimum overall frequency of 2.1% (11 of 519) for germline MMR defects ascertained through EC in the index patients. The fact that only two of 23 families with site-specific EC (8.7%) had germline mutations in MMR genes suggests another as yet unknown etiology in most families with site-specific EC.

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