caa a22 4500 445331453 CHVBK 20180317142738.0 cr unu---uuuuu 170323e20110601xx s 000 0 eng 10.1007/s10689-011-9419-0 doi (NATIONALLICENCE)springer-10.1007/s10689-011-9419-0 Identification and surveillance of 19 Lynch syndrome families in southern Italy: report of six novel germline mutations and a common founder mutation [Elektronische Daten] [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. Springer Science+Business Media B.V., 2011 Lynch syndrome nationallicence Apulia nationallicence HNPCC nationallicence Surveillance nationallicence MLH1 nationallicence MSH2 nationallicence Founder effect nationallicence HNPCC : Hereditary non polyposis colorectal cancer nationallicence MMR : Mismatch repair nationallicence CRC : Colorectal cancer nationallicence LS : Lynch syndrome nationallicence MSI : Microsatellite instability nationallicence AC : Amsterdam criteria nationallicence BG : Bethesda guidelines nationallicence RBG : Revised Bethesda guidelines nationallicence IHC : Immunohistochemistry nationallicence MTS : Muir-Torre syndrome nationallicence DHPLC : Denaturing high pressure liquid chromatography nationallicence MLPA : Multiplex ligation-dependent probe amplification nationallicence InSIGHT : International society for gastrointestinal hereditary tumors nationallicence Lastella Patrizia UOC Genetica Medica-Dipartimento di Biomedicina dell‘Età Evolutiva-Università di Bari "Aldo Moro” Azienda, Ospedaliero-Universitaria Policlinico P.zza G. Cesare 11, 70124, Bari, Italy aut Patruno Margherita UOC Genetica Medica-Dipartimento di Biomedicina dell‘Età Evolutiva-Università di Bari "Aldo Moro” Azienda, Ospedaliero-Universitaria Policlinico P.zza G. Cesare 11, 70124, Bari, Italy aut Forte Giovanna UOC Genetica Medica-Dipartimento di Biomedicina dell‘Età Evolutiva-Università di Bari "Aldo Moro” Azienda, Ospedaliero-Universitaria Policlinico P.zza G. Cesare 11, 70124, Bari, Italy aut Montanaro Alba UOC Chirurgia Generale "C. Righetti” Università di Bari "Aldo Moro”, Azienda Ospedaliero-Universitaria Policlinico, Bari, Italy aut Di Gregorio Carmela Dipartimento ad Attività Integrata di Laboratori, Anatomia Patologica e Medicina Legale, Sezione di Anatomia Patologica, Azienda Ospedaliero Universitaria Policlinico di Modena, Modena, Italy aut Sabbà Carlo UOC Geriatria e Gerontologia Università di Bari "Aldo Moro”, Azienda Ospedaliero-Universitaria Policlinico, Bari, Italy aut Suppressa Patrizia UOC Geriatria e Gerontologia Università di Bari "Aldo Moro”, Azienda Ospedaliero-Universitaria Policlinico, Bari, Italy aut Piepoli Adalgisa Gastroenterology Unit and Research Laboratory, Casa Sollievo della Sofferenza, Hospital, IRCCS, San Giovanni Rotondo, Italy aut Panza Anna Gastroenterology Unit and Research Laboratory, Casa Sollievo della Sofferenza, Hospital, IRCCS, San Giovanni Rotondo, Italy aut Andriulli Angelo Gastroenterology Unit and Research Laboratory, Casa Sollievo della Sofferenza, Hospital, IRCCS, San Giovanni Rotondo, Italy aut Resta Nicoletta UOC Genetica Medica-Dipartimento di Biomedicina dell‘Età Evolutiva-Università di Bari "Aldo Moro” Azienda, Ospedaliero-Universitaria Policlinico P.zza G. Cesare 11, 70124, Bari, Italy aut Stella Alessandro UOC Genetica Medica-Dipartimento di Biomedicina dell‘Età Evolutiva-Università di Bari "Aldo Moro” Azienda, Ospedaliero-Universitaria Policlinico P.zza G. Cesare 11, 70124, Bari, Italy aut Familial Cancer Springer Netherlands 10/2(2011-06-01), 285-295 1389-9600 10:2<285 2011 10 10689 https://doi.org/10.1007/s10689-011-9419-0 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10689-011-9419-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Lastella Patrizia UOC Genetica Medica-Dipartimento di Biomedicina dell‘Età Evolutiva-Università di Bari "Aldo Moro” Azienda, Ospedaliero-Universitaria Policlinico P.zza G. Cesare 11, 70124, Bari, Italy aut NATIONALLICENCE 700 1- Patruno Margherita UOC Genetica Medica-Dipartimento di Biomedicina dell‘Età Evolutiva-Università di Bari "Aldo Moro” Azienda, Ospedaliero-Universitaria Policlinico P.zza G. Cesare 11, 70124, Bari, Italy aut NATIONALLICENCE 700 1- Forte Giovanna UOC Genetica Medica-Dipartimento di Biomedicina dell‘Età Evolutiva-Università di Bari "Aldo Moro” Azienda, Ospedaliero-Universitaria Policlinico P.zza G. Cesare 11, 70124, Bari, Italy aut NATIONALLICENCE 700 1- Montanaro Alba UOC Chirurgia Generale "C. Righetti” Università di Bari "Aldo Moro”, Azienda Ospedaliero-Universitaria Policlinico, Bari, Italy aut NATIONALLICENCE 700 1- Di Gregorio Carmela Dipartimento ad Attività Integrata di Laboratori, Anatomia Patologica e Medicina Legale, Sezione di Anatomia Patologica, Azienda Ospedaliero Universitaria Policlinico di Modena, Modena, Italy aut NATIONALLICENCE 700 1- Sabbà Carlo UOC Geriatria e Gerontologia Università di Bari "Aldo Moro”, Azienda Ospedaliero-Universitaria Policlinico, Bari, Italy aut NATIONALLICENCE 700 1- Suppressa Patrizia UOC Geriatria e Gerontologia Università di Bari "Aldo Moro”, Azienda Ospedaliero-Universitaria Policlinico, Bari, Italy aut NATIONALLICENCE 700 1- Piepoli Adalgisa Gastroenterology Unit and Research Laboratory, Casa Sollievo della Sofferenza, Hospital, IRCCS, San Giovanni Rotondo, Italy aut NATIONALLICENCE 700 1- Panza Anna Gastroenterology Unit and Research Laboratory, Casa Sollievo della Sofferenza, Hospital, IRCCS, San Giovanni Rotondo, Italy aut NATIONALLICENCE 700 1- Andriulli Angelo Gastroenterology Unit and Research Laboratory, Casa Sollievo della Sofferenza, Hospital, IRCCS, San Giovanni Rotondo, Italy aut NATIONALLICENCE 700 1- Resta Nicoletta UOC Genetica Medica-Dipartimento di Biomedicina dell‘Età Evolutiva-Università di Bari "Aldo Moro” Azienda, Ospedaliero-Universitaria Policlinico P.zza G. Cesare 11, 70124, Bari, Italy aut NATIONALLICENCE 700 1- Stella Alessandro UOC Genetica Medica-Dipartimento di Biomedicina dell‘Età Evolutiva-Università di Bari "Aldo Moro” Azienda, Ospedaliero-Universitaria Policlinico P.zza G. Cesare 11, 70124, Bari, Italy aut NATIONALLICENCE 773 0- Familial Cancer Springer Netherlands 10/2(2011-06-01), 285-295 1389-9600 10:2<285 2011 10 10689 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer