scholarly journals A Mononucleotide Markers Panel to Identify hMLH1/hMSH2 Germline Mutations

2007 ◽  
Vol 23 (3) ◽  
pp. 179-187 ◽  
Author(s):  
M. Pedroni ◽  
B. Roncari ◽  
S. Maffei ◽  
L. Losi ◽  
A. Scarselli ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Autosomal Dominant ◽  
Germline Mutations ◽  
Cell Replication ◽  
Cost Effectiveness Ratio ◽  
Hereditary Nonpolyposis ◽  
Dominant Disease ◽  
Almost All ◽  
The Cost

Hereditary NonPolyposis Colorectal Cancer (Lynch syndrome) is an autosomal dominant disease caused by germline mutations in a class of genes deputed to maintain genomic integrity during cell replication, mutations result in a generalized genomic instability, particularly evident at microsatellite loci (Microsatellite Instability, MSI). MSI is present in 85–90% of colorectal cancers that occur in Lynch Syndrome. To standardize the molecular diagnosis of MSI, a panel of 5 microsatellite markers was proposed (known as the “Bethesda panel”). Aim of our study is to evaluate if MSI testing with two mononucleotide markers, such as BAT25 and BAT26, was sufficient to identify patients withhMLH1/hMSH2germline mutations. We tested 105 tumours for MSI using both the Bethesda markers and the two mononucleotide markers BAT25 and BAT26. Moreover, immunohistochemical evaluation of MLH1 and MSH2 proteins was executed on the tumours with at least one unstable microsatellite, whereas germlinehMLH1/hMSH2mutations were searched for all cases showing two or more unstable microsatellites.The Bethesda panel detected more MSI(+) tumors than the mononucleotide panel (49.5% and 28.6%, respectively). However, the mononucleotide panel was more efficient to detect MSI(+) tumours with lack of expression of Mismatch Repair proteins (93% vs 54%). Germline mutations were detected in almost all patients whose tumours showed MSI and no expression of MLH1/MSH2 proteins. No germline mutations were found in patients with MSI(+) tumour defined only through dinucleotide markers. In conclusion, the proposed mononucleotide markers panel seems to have a higher predictive value to identifyhMLH1andhMSH2mutation-positive patients with Lynch syndrome. Moreover, this panel showed increased specificity, thus improving the cost/effectiveness ratio of the biomolecular analyses.

scholarly journals Muir-Torre Syndrome: The Importance of a Detailed Family History

2019 ◽  
Vol 10 (2) ◽  
pp. 180-185
Author(s):  
Christopher K.H. Burris ◽  
Maria E. Rodriguez ◽  
Meisha L. Raven ◽  
Devasis N. Reddy ◽  
Yaohui G. Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Family History ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Autosomal Dominant ◽  
Skin Neoplasms ◽  
Skin Lesions ◽  
Hereditary Nonpolyposis ◽  
Detailed Family History ◽  
Dominant Disease ◽  
Typical Skin

Muir-Torre syndrome, a variant of Lynch syndrome or hereditary nonpolyposis colorectal cancer, is an autosomal dominant disease characterized by skin neoplasms (sebaceous or keratoacanthomas) and visceral malignancies. Due to the rarity of the syndrome there are no firm guidelines on how and when to test patients with its typical skin lesions. We describe a case that highlights the importance of a detailed family history.

scholarly journals Differential diagnosis of small bowel occlusions

2009 ◽  
Vol 3 (2) ◽  
pp. 81-87
Author(s):  
Paolo Ghiringhelli
Keyword(s):  
Colorectal Cancer ◽  
Differential Diagnosis ◽  
Lynch Syndrome ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Autosomal Dominant ◽  
Age At Onset ◽  
Clinical Manifestations ◽  
Early Age ◽  
Increased Risk ◽  
Hereditary Nonpolyposis

Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is a common autosomal dominant syndrome characterized by early age at onset, and microsatellite instability (MSI). Patients with Lynch syndrome have a markedly increased risk of colorectal cancer. We report a case of a 28-year-old male with Lynch syndrome; the case allows to describe clinical manifestations and diagnostic criteria of this syndrome, and to underline the importance of genetics in the diagnosis of this disease.

scholarly journals Hereditary Nonpolyposis Colorectal Cancer (HNPCC)/Lynch Syndrome

2013 ◽  
Author(s):  
Verena Steinke ◽  
Christoph Engel ◽  
Reinhard Büttner ◽  
Hans Konrad Schackert ◽  
Wolff H. Schmiegel ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Hereditary Nonpolyposis

scholarly journals Missed Adenomas during Colonoscopic Surveillance in Individuals with Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer)

2008 ◽  
Vol 1 (6) ◽  
pp. 470-475 ◽  
Author(s):  
Elena M. Stoffel ◽  
D. Kim Turgeon ◽  
David H. Stockwell ◽  
Lili Zhao ◽  
Daniel P. Normolle ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Colonoscopic Surveillance ◽  
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.

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