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01-06-2011

Identification and surveillance of 19 Lynch syndrome families in southern Italy: report of six novel germline mutations and a common founder mutation

Authors: Patrizia Lastella, Margherita Patruno, Giovanna Forte, Alba Montanaro, Carmela Di Gregorio, Carlo Sabbà, Patrizia Suppressa, Adalgisa Piepoli, Anna Panza, Angelo Andriulli, Nicoletta Resta, Alessandro Stella

Published in: Familial Cancer | Issue 2/2011

Abstract

Lynch syndrome (LS), or hereditary non-polyposis colorectal cancer (HNPCC), is an autosomal dominant condition responsible for early onset cancer mostly in the colonrectum and endometrium as well as in other organ sites. Lynch syndrome is caused by germline mutations in mismatch repair genes, prevalently in hMSH2, hMLH1, and less frequently in hMSH6 and hPMS2. Twenty-nine non-related index cases with colorectal cancer (CRC) were collected from a region in southeast Italy (Apulia). Among this set of patients, fifteen fulfilled the Amsterdam criteria II. The presence of tumor microsatellite instability (MSI) was assessed in all index cases and 19 (15 AC+/4 AC−) were classified as MSI-H. Mutation analysis performed on all patients, identified 15 pathogenic mutations in hMLH1 and 4 in hMSH2. 4/15 mutations in hMLH1 and 2/4 hMSH2 mutations have not been previously reported. Three previously reported mutations were further investigated for the possibility of a common founder effect. Genetic counseling was offered to all probands and extended to 183 relatives after molecular testing and 85 (46%) mutation carriers were identified. Eighty mutation carriers underwent an accurate clinical and instrumental surveillance protocol. Our results confirm that the identification of LS patients based exclusively on family history may miss patients carrying germline mutations in the MMR genes. Moreover, our results demonstrated that molecular screening and subsequent instrumental surveillance are very effective in identifying CRCs at earlier stages and reducing the number of deaths from secondary cancers in HNPCC patients.

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Title: Identification and surveillance of 19 Lynch syndrome families in southern Italy: report of six novel germline mutations and a common founder mutation
Authors: Patrizia Lastella
Margherita Patruno
Giovanna Forte
Alba Montanaro
Carmela Di Gregorio
Carlo Sabbà
Patrizia Suppressa
Adalgisa Piepoli
Anna Panza
Angelo Andriulli
Nicoletta Resta
Alessandro Stella
Publication date: 01-06-2011
Publisher: Springer Netherlands
Published in: Familial Cancer / Issue 2/2011
Print ISSN: 1389-9600
Electronic ISSN: 1573-7292
DOI: https://doi.org/10.1007/s10689-011-9419-0

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