P Watson

Publications (2)30.32 Total impact

• Article: Analysis of mismatch repair genes in hereditary non-polyposis colorectal cancer patients.

  B Liu, R Parsons, N Papadopoulos, N C Nicolaides, H T Lynch, P Watson, J R Jass, M Dunlop, A Wyllie, P Peltomäki, A de la Chapelle, S R Hamilton, B Vogelstein, K W Kinzler
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  ABSTRACT: Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant disorder characterized by the early onset of colorectal cancer and linked to germline defects in at least four mismatch repair genes. Although much has been learned about the molecular pathogenesis of this disease, questions related to effective presymptomatic diagnosis are largely unanswered because of its genetic complexity. In this study, we evaluated tumors from 74 HNPCC kindreds for genomic instability characteristic of a mismatch repair deficiency and found such instability in 92% of the kindreds. The entire coding regions of the five known human mismatch repair genes were evaluated in 48 kindreds with instability, and mutations were identified in 70%. This study demonstrates that a combination of techniques can be used to genetically diagnose tumor susceptibility in the majority of HNPCC kindreds and lays the foundation for genetic testing of this relatively common disease.
  Nature Medicine 03/1996; 2(2):169-74. · 22.46 Impact Factor
• Source

  Available from: aacrjournals.org

  Article: hMSH2 mutations in hereditary nonpolyposis colorectal cancer kindreds.

  B Liu, R E Parsons, S R Hamilton, G M Petersen, H T Lynch, P Watson, S Markowitz, J K Willson, J Green, A de la Chapelle
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  ABSTRACT: It has recently been shown that hereditary nonpolyposis colorectal cancer (HNPCC) is caused by hereditable defects in DNA mismatch repair genes. However, the fraction of HNPCC due to defects in any one repair gene and the nature of these mutations are not known. We analyzed 29 HNPCC kindreds for mutations in the prototype DNA mismatch repair gene hMSH2 by a combination of linkage analysis, polymerase chain reaction-based screening, and sequencing of the coding region. The complete intron/exon structure of the gene was ascertained to facilitate this analysis. The results suggest that at least 40% of classic HNPCC kindreds are associated with germline mutations in hMSH2 and that most of these mutations produce drastic alterations in the predicted protein product.
  Cancer Research 10/1994; 54(17):4590-4. · 7.86 Impact Factor