Familial Cancer

, Volume 10, Issue 2, pp 285–295 | Cite as

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

  • 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


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.


Lynch syndrome Apulia HNPCC Surveillance MLH1 MSH2 Founder effect 



Hereditary non polyposis colorectal cancer


Mismatch repair


Colorectal cancer


Lynch syndrome


Microsatellite instability


Amsterdam criteria


Bethesda guidelines


Revised Bethesda guidelines




Muir-Torre syndrome


Denaturing high pressure liquid chromatography


Multiplex ligation-dependent probe amplification


International society for gastrointestinal hereditary tumors



Supported by grants: (a) Regione Puglia contract PE 041CARSO Ricerca Oncologica; (b) Fondazione Cassa di Risparmio di Puglia “Identificazione di eventi di splicing associati ai tumori del colon retto” and (c) Ricerca Finalizzata Università di Bari (60%) all to AS. The authors wish to thank Clare Hannon (Bsc Hons) and Gennaro Lenato (PhD) for their careful editing and critical reading of the manuscript.


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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Patrizia Lastella
    • 1
  • Margherita Patruno
    • 1
  • Giovanna Forte
    • 1
  • Alba Montanaro
    • 2
  • Carmela Di Gregorio
    • 3
  • Carlo Sabbà
    • 4
  • Patrizia Suppressa
    • 4
  • Adalgisa Piepoli
    • 5
  • Anna Panza
    • 5
  • Angelo Andriulli
    • 5
  • Nicoletta Resta
    • 1
  • Alessandro Stella
    • 1
  1. 1.UOC Genetica Medica-Dipartimento di Biomedicina dell‘Età Evolutiva-Università di Bari “Aldo Moro” AziendaBariItaly
  2. 2.UOC Chirurgia Generale “C. Righetti” Università di Bari “Aldo Moro”Azienda Ospedaliero-Universitaria PoliclinicoBariItaly
  3. 3.Dipartimento ad Attività Integrata di Laboratori, Anatomia Patologica e Medicina Legale, Sezione di Anatomia PatologicaAzienda Ospedaliero Universitaria Policlinico di ModenaModenaItaly
  4. 4.UOC Geriatria e Gerontologia Università di Bari “Aldo Moro”Azienda Ospedaliero-Universitaria PoliclinicoBariItaly
  5. 5.Gastroenterology Unit and Research LaboratoryCasa Sollievo della Sofferenza, Hospital, IRCCSSan Giovanni RotondoItaly

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