Mean age of tumor onset in hereditary nonpolyposis colorectal cancer (HNPCC) families correlates with the presence of mutations in DNA hismatch repair genes

Valeria Pensotti, Paolo Radice, Silvano Presciuttini, Daniele Calistri, Isabella Gazzoli, Ana Paula Grimalt Perez, Patrizia Mondini, Giovanni Buonsanti, Paola Sala, Carlo Rossetti, Guglielmina N. Ranzani, Lucio Bertario, Marco A. Pierotti

Research output: Contribution to journalArticle

Abstract

Fourteen Italian families affected with hereditary nonpolyposis colorectal cancer (HNPCC) were screened for germline mutations at three DNA mismatch repair (MMR) genes, MSH2, MLHI, and GTBP, by using a combination of different methods that included an in vitro synthesized protein assay, single-strand conformation polymorphism analysis, and direct sequencing. DNA alterations were observed in six instances, including a single base deletion in MSH2 exon 14, an A-to-G transition in the splice donor site of MLHI exon 6, and two missense mutations in MLHI exons 5 and 9. A previously reported common mutation affecting the splice donor site of MSH2 exon 5 was identified in two families. No mutations were detected in the GTBP gene. In total, eight of 16 Italian HNPCC families (50%), including two previously reported kindreds, were found to carry a mutation in MMR genes. We compared the mean age of colorectal cancer onset in the index cases (three patients for each family) between the two groups of kindreds, those with identified mutation vs. those without, and found that the first had a significantly lower value (43.0 vs. 53.7 years, P = 0.014). This finding suggests that HNPCC families with a more advanced age of tumor onset are less likely to he associated with known MMR genes.

Original languageEnglish
Pages (from-to)135-142
Number of pages8
JournalGenes Chromosomes and Cancer
Volume19
Issue number3
DOIs
Publication statusPublished - 1997

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

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