The frequency of previously undetectable deletions involving 3′ Exons of the PMS2 gene. Issue 1 (25th September 2012)

• Record Type: Journal Article
• Authors: Vaughn, Cecily P.; Baker, Christine L.; Samowitz, Wade S.; Swensen, Jeffrey J.
• Is Part Of: Genes, chromosomes & cancer. Volume 52:Issue 1(2013:Jan.)
• Page Start: 107
• Page End: 112
• Publication Date: 2012-09-25
• Subjects: Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22011
• Languages: English
• ISSNs: 1045-2257

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Lynch syndrome is characterized by mutations in one of four mismatch repair genes, <italic>MLH1</italic>, <italic>MSH2</italic>, <italic>MSH6</italic>, or <italic>PMS2</italic>. Clinical mutation analysis of these genes includes sequencing of exonic regions and deletion/duplication analysis. However, detection of deletions and duplications in <italic>PMS2</italic> has previously been confined to Exons 1–11 due to gene conversion between <italic>PMS2</italic> and the pseudogene <italic>PMS2CL</italic> in the remaining 3′ exons (Exons 12–15). We have recently described an MLPA‐based method that permits detection of deletions of <italic>PMS2</italic> Exons 12–15; however, the frequency of such deletions has not yet been determined. To address this question, we tested for 3′ deletions in 58 samples that were reported to be negative for <italic>PMS2</italic> mutations using previously available methods. All samples were from individuals whose tumors exhibited loss of PMS2 immunohistochemical staining without concomitant loss of MLH1 immunostaining. We identified seven samples in this cohort with deletions in the 3′ region of <italic>PMS2</italic>, including three previously reported samples with deletions of Exons 13–15 (two samples) and Exons 14–15. Also detected were deletions of Exons 12–15, Exon 13, and Exon 14 (two samples). Breakpoint analysis of the intragenic deletions suggests they occurred through <italic>Alu</italic>‐mediated recombination. Our results indicate that ∼12% of samples suspected of harboring a <italic>PMS2</italic> mutation based on immunohistochemical staining, for which mutations have not yet been identified, would benefit from testing using the new methodology. © 2012 Wiley Periodicals, Inc.</p> </abstract>