OBJECTIVE: Identification of clinical and molecular characteristics associated with constitutional MLH1 and MSH2 mutations and definition of a stepwise strategy for the selection of colorectal cancer (CRC) patients amenable to MLH1 and MSH2 genetic testing. METHODS: 90 unrelated CRC patients were initially selected on the basis of either familial or early onset occurrence of CRC. They were screened for the presence of constitutional MLH1 and MSH2 mutations and for microsatellite instability (MSI). RESULTS: 16 pathogenetic mutations (9 MLH1 and 7 MSH2) were identified in 41% of Amsterdam hereditary nonpolyposis colorectal cancer (HNPCC) families, 5% of suspected HNPCC families, and 14% of sporadic early-onset CRC patients. The presence of the mutations correlated with MSI, with early age of onset and proximal location of the tumor, and with the presence of some extracolonic tumors of the HNPCC spectrum and/or multiple tumors in the family. CONCLUSIONS: Evaluation of clinical and molecular characteristics is useful for the identification of candidates to MLH1 and MSH2 mutational analysis and allows the application of a rational approach to genetic testing.
OBJECTIVE: Identification of clinical and molecular characteristics associated with constitutional MLH1 and MSH2 mutations and definition of a stepwise strategy for the selection of colorectal cancer (CRC) patients amenable to MLH1 and MSH2 genetic testing. METHODS: 90 unrelated CRCpatients were initially selected on the basis of either familial or early onset occurrence of CRC. They were screened for the presence of constitutional MLH1 and MSH2 mutations and for microsatellite instability (MSI). RESULTS: 16 pathogenetic mutations (9 MLH1 and 7 MSH2) were identified in 41% of Amsterdam hereditary nonpolyposis colorectal cancer (HNPCC) families, 5% of suspected HNPCC families, and 14% of sporadic early-onset CRCpatients. The presence of the mutations correlated with MSI, with early age of onset and proximal location of the tumor, and with the presence of some extracolonic tumors of the HNPCC spectrum and/or multiple tumors in the family. CONCLUSIONS: Evaluation of clinical and molecular characteristics is useful for the identification of candidates to MLH1 and MSH2 mutational analysis and allows the application of a rational approach to genetic testing.
Authors: Jerneja Tomsic; Sandya Liyanarachchi; Heather Hampel; Monika Morak; Brittany C Thomas; Victoria M Raymond; Anu Chittenden; Hans K Schackert; Stephen B Gruber; Sapna Syngal; Alessandra Viel; Elke Holinski-Feder; Stephen N Thibodeau; Albert de la Chapelle Journal: Int J Cancer Date: 2011-08-30 Impact factor: 7.396
Authors: E Lucci-Cordisco; V Rovella; S Carrara; A Percesepe; M Pedroni; A Bellacosa; O Caluseriu; M Forasarig; M Anti; G Neri; M Ponz de Leon; A Viel; M Genuardi Journal: Fam Cancer Date: 2001 Impact factor: 2.375
Authors: M Aronson; C Swallow; A Govindarajan; K Semotiuk; Z Cohen; P Kaurah; L Velsher; I Ambus; K Buckley; C Forster-Gibson; W S Meschino; A Blumenthal; R H Kim; S Brar Journal: Curr Oncol Date: 2020-05-01 Impact factor: 3.677
Authors: M Ponz de Leon; P Benatti; C Di Gregorio; M Pedroni; L Losi; M Genuardi; A Viel; M Fornasarig; E Lucci-Cordisco; M Anti; G Ponti; F Borghi; I Lamberti; L Roncucci Journal: Br J Cancer Date: 2004-02-23 Impact factor: 7.640
Authors: Maartje Nielsen; Noel F C C de Miranda; Marjo van Puijenbroek; Ekaterina S Jordanova; Anneke Middeldorp; Tom van Wezel; Ronald van Eijk; Carli M J Tops; Hans F A Vasen; Frederik J Hes; Hans Morreau Journal: BMC Cancer Date: 2009-06-15 Impact factor: 4.430