𝔖 Bobbio Scriptorium
✦   LIBER   ✦

Evaluation of enzymatic mutation detection™ in hereditary nonpolyposis colorectal cancer

✍ Scribed by Robyn Otway; Natasha Tetlow; June Hornby; Maija Kohonen-Corish

Publisher
John Wiley and Sons
Year
2000
Tongue
English
Weight
242 KB
Volume
16
Category
Article
ISSN
1059-7794

No coin nor oath required. For personal study only.

✦ Synopsis

In hereditary nonpolyposis colorectal cancer (HNPCC), the majority of reported mutations are dispersed throughout the 35 exons of the two principal susceptibility genes, MLH1 and MSH2, and because of this complexity, rapid mutation screening methods are required. The aim of this study was to evaluate the sensitivity of the Enzymatic Mutation Detection™ (EMD™) assay in HNPCC using genomic DNA samples with known gene alterations in MLH1 and MSH2. The EMD assay relies upon the enzyme T4 Endonuclease VII recognizing and cleaving DNA mismatches, created when a PCR product containing a sequence alteration is hybridized with a wild type probe. A total of 68 different sequence variants from 30 exons were analyzed. The EMD assay was able to detect 62 of the 68 sequence variants (91%) with the majority showing strong cleavage products. One of the advantages of the EMD assay over other mutation screening techniques is that larger fragments can be analyzed in a single assay. No specialized equipment is required and one set of primers is sufficient for radioactive detection of the cleavage products. This method can be adapted to use fluorescent dye-labelled primers and may be automated to detect mutations accurately and rapidly in a large number of samples. One new MLH1 mutation (418delA) and two novel MSH2 mutations (1A>C; 227-228delAG) were also detected in HNPCC patients screened using this method. Hum Mutat 16:61-67, 2000.

📜 SIMILAR VOLUMES

Influence of selection criteria on mutat
Influence of selection criteria on mutation detection in patients with hereditary nonpolyposis colorectal cancer
✍ Karl Heinimann; Rodney J. Scott; Jean-Marie Buerstedde; Walter Weber; Karl Siebo 📂 Article 📅 1999 🏛 John Wiley and Sons 🌐 English ⚖ 109 KB 👁 1 views

## BACKGROUND. Hereditary nonpolyposis colorectal cancer (HNPCC) is linked genetically to mutations in DNA mismatch repair (MMR) genes. Because a deficiency in MMR does not predict a specific phenotype, the original selection criteria may be too restrictive in identifying additional families. The

Characterization of MSH2 and MLH1 mutati
Characterization of MSH2 and MLH1 mutations in Italian families with hereditary nonpolyposis colorectal cancer
✍ Alessandra Viel; Maurizio Genuardi; Eugenia Capozzi; Francesca Leonardi; Alfonso 📂 Article 📅 1997 🏛 John Wiley and Sons 🌐 English ⚖ 331 KB 👁 2 views

Mismatch repair genes MSH2 and MLH1 are considered to be the two major genes that are responsible for hereditary nonpolyposis colorectal cancer (HNPCC). Germline heterozygous inactivating mutations of MSH2 and MLH1 have been identified previously in a substantial fraction of individuals who are pred

Clinical challenges in management of fam
Clinical challenges in management of familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer
✍ Patrick M. Lynch 📂 Article 📅 1999 🏛 John Wiley and Sons 🌐 English ⚖ 107 KB 👁 2 views

A s of 1999, it is possible to test selected subjects for carriage of germline mutations in genes responsible for familial adenomatous polyposis (FAP), 1,2 hereditary nonpolyposis colorectal cancer (HNPCC), 3,4 Peutz-Jeghers syndrome, 5 and juvenile polyposis. 6,7 These diseases are heterogeneous ph

Hereditary nonpolyposis colorectal cance
Hereditary nonpolyposis colorectal cancer: Identification of novel germline mutations in two kindreds not fulfilling the Amsterdam criteria
✍ Barbara Quaresima; Cristina Grandinetti; Francesco Baudi; PierFrancesco Tassone; 📂 Article 📅 1998 🏛 John Wiley and Sons 🌐 English ⚖ 104 KB 👁 2 views

Hunter syndrome is an X-linked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS). The IDS deficiency can be caused by several different types of mutations in the IDS gene. We have performed a molecular and mutation analysis of a total of 19 unrelat

Mutation sharing, predominant involvemen
Mutation sharing, predominant involvement of the MLH1 gene and description of four novel mutations in hereditary nonpolyposis colorectal cancer
✍ Mari Holmberg; Paula Kristo; Robert B. Chadwicks; Jukka-Pekka Mecklin; Heikki Jä 📂 Article 📅 1998 🏛 John Wiley and Sons 🌐 English ⚖ 37 KB 👁 2 views

Worldwide, the DNA mismatch repair genes MSH2 and MLH1 account for a major share and almost equal proportions of hereditary nonpolyposis colorectal cancer (HNPCC). Furthermore, the predisposing mutation usually varies from kindred to kindred. In this study, we screened 29 verified or putative HNPCC

MLH1 and MSH2 constitutinal mutations in
MLH1 and MSH2 constitutinal mutations in colorectal cancer families not meeting the standard criteria for hereditary nonpolyposis colorectal cancer
✍ Maurizio Genuardi; Marcello Anti; Eugenia Capozzi; Francesca Leonardi; Mara Forn 📂 Article 📅 1998 🏛 John Wiley and Sons 🌐 French ⚖ 67 KB 👁 2 views

## Genetic diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC ) may have a significant impact on the clinical management of patients and their at-risk relatives. At present, clinical criteria represent the simplest and most useful method for the identification of HNPCC families and for