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Long-range PCR facilitates the identification of PMS2-specific mutations

โœ Scribed by Mark Clendenning; Heather Hampel; Jennifer LaJeunesse; Annika Lindblom; Jan Lockman; Mef Nilbert; Leigha Senter; Kaisa Sotamaa; Albert de la Chapelle

Book ID
102259290
Publisher
John Wiley and Sons
Year
2006
Tongue
English
Weight
222 KB
Volume
27
Category
Article
ISSN
1059-7794

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โœฆ Synopsis

Communicated by Graham R. Taylor

Mutations within the DNA mismatch repair gene, ''postmeiotic segregation increased 2'' (PMS2), have been associated with a predisposition to hereditary nonpolyposis colorectal cancer (HNPCC; Lynch syndrome). The presence of a large family of highly homologous PMS2 pseudogenes has made previous attempts to sequence PMS2 very difficult. Here, we describe a novel method that utilizes long-range PCR as a way to preferentially amplify PMS2 and not the pseudogenes. A second, exon-specific, amplification from diluted long-range products enables us to obtain a clean sequence that shows no evidence of pseudogene contamination. This method has been used to screen a cohort of patients whose tumors were negative for the PMS2 protein by immunohistochemistry and had not shown any mutations within the MLH1 gene. Sequencing of the PMS2 gene from 30 colorectal and 11 endometrial cancer patients identified 10 novel sequence changes as well as 17 sequence changes that had previously been identified. In total, putative pathologic mutations were detected in 11 of the 41 families. Among these were five novel mutations, c.70511G4T, c.736_741del6ins11, c.862_863del, c.1688G4T, and c.2007-1G4A. We conclude that PMS2 mutation detection in selected Lynch syndrome and Lynch syndrome-like patients is both feasible and desirable. Hum Mutat 27(5), 490-495, 2006.

๐Ÿ“œ SIMILAR VOLUMES

Long-range PCR facilitates the identific
Long-range PCR facilitates the identification of PMS2-specific mutations
โœ Mark Clendenning; Heather Hampel; Jennifer LaJeunesse; Annika Lindblom; Jan Lock ๐Ÿ“‚ Article ๐Ÿ“… 2006 ๐Ÿ› John Wiley and Sons ๐ŸŒ English โš– 82 KB

The original article to which this Erratum refers was published in Human Mutation 27(5): 490-495 (2006). On page 491 in Figure 1C, and on page 494 in Table 2, the c.736\_741del6ins11 mutation results in the protein variant p.P246CfsX3. It was incorrectly written as p.P246CfsX7.

Identification of Lynch syndrome mutatio
Identification of Lynch syndrome mutations in the MLH1โ€“PMS2 interface that disturb dimerization and mismatch repair
โœ Jan Kosinski; Inga Hinrichsen; Janusz M. Bujnicki; Peter Friedhoff; Guido Plotz ๐Ÿ“‚ Article ๐Ÿ“… 2010 ๐Ÿ› John Wiley and Sons ๐ŸŒ English โš– 423 KB ๐Ÿ‘ 2 views

Missense alterations of the mismatch repair gene MLH1 have been identified in a significant proportion of individuals suspected of having Lynch syndrome, a hereditary syndrome that predisposes for cancer of colon and endometrium. The pathogenicity of many of these alterations, however, is unclear. A