BACKGROUND: Colorectal cancer is a common cancer worldwide, with 5-10% of cases being hereditary. Familial adenomatous polyposis syndrome (FAP) is caused by germline mutations in the APC gene or rarely in the MUTYH gene. PATIENTS AND METHODS: This work did not identify germline mutations in the MUTYH, NTHL1, POLD1 and POLE genes in 15 individuals belonging to five families with classic FAP, who had the mutation in the APC gene confirmed in a previous study. Our results support mutations in the APC gene as the main genetic contribution of classical FAP with severe phenotype. In the family that had the most aggressive form of the disease, we performed an array-based Comparative Genomic Hybridization analysis and identified the germinal loss of an allele of the NOTCH2 and BMPR2 genes in the mother (proband) and daughter. In order to validate the involvement of these genes in the other four families of this study, we analyzed the DNA copy number variation in the peripheral blood of the 15 participants. RESULTS: FAP is a syndrome with considerable genetic and phenotypic heterogeneity and this phenomenon may explain the presence of secondary genetic alterations, such as the allelic loss of NOTCH2 and BMPR2 genes, found only in one family in this study. The CNV analysis confirmed that only the two members of the FAP2 family (patient 02H and 02F) had a deletion of these two genes, as the aCGH methodology had found. The other study participants did not show allelic loss for these two genes. CONCLUSION: Validation in a larger number of families could confirm the presence of these new genetic alterations in classic FAP and improve understanding of the different types of aggressiveness of the disease. Copyright 2022, International Institute of Anticancer Research.
BACKGROUND: Colorectal cancer is a common cancer worldwide, with 5-10% of cases being hereditary. Familial adenomatous polyposis syndrome (FAP) is caused by germline mutations in the APC gene or rarely in the MUTYH gene. PATIENTS AND METHODS: This work did not identify germline mutations in the MUTYH, NTHL1, POLD1 and POLE genes in 15 individuals belonging to five families with classic FAP, who had the mutation in the APC gene confirmed in a previous study. Our results support mutations in the APC gene as the main genetic contribution of classical FAP with severe phenotype. In the family that had the most aggressive form of the disease, we performed an array-based Comparative Genomic Hybridization analysis and identified the germinal loss of an allele of the NOTCH2 and BMPR2 genes in the mother (proband) and daughter. In order to validate the involvement of these genes in the other four families of this study, we analyzed the DNA copy number variation in the peripheral blood of the 15 participants. RESULTS: FAP is a syndrome with considerable genetic and phenotypic heterogeneity and this phenomenon may explain the presence of secondary genetic alterations, such as the allelic loss of NOTCH2 and BMPR2 genes, found only in one family in this study. The CNV analysis confirmed that only the two members of the FAP2 family (patient 02H and 02F) had a deletion of these two genes, as the aCGH methodology had found. The other study participants did not show allelic loss for these two genes. CONCLUSION: Validation in a larger number of families could confirm the presence of these new genetic alterations in classic FAP and improve understanding of the different types of aggressiveness of the disease. Copyright 2022, International Institute of Anticancer Research.
Authors: Robbert D A Weren; Marjolijn J L Ligtenberg; C Marleen Kets; Richarda M de Voer; Eugène T P Verwiel; Liesbeth Spruijt; Wendy A G van Zelst-Stams; Marjolijn C Jongmans; Christian Gilissen; Jayne Y Hehir-Kwa; Alexander Hoischen; Jay Shendure; Evan A Boyle; Eveline J Kamping; Iris D Nagtegaal; Bastiaan B J Tops; Fokko M Nagengast; Ad Geurts van Kessel; J Han J M van Krieken; Roland P Kuiper; Nicoline Hoogerbrugge Journal: Nat Genet Date: 2015-05-04 Impact factor: 38.330
Authors: Aedan Roberts; Derek Nancarrow; Mark Clendenning; Daniel D Buchanan; Mark A Jenkins; David Duggan; Darin Taverna; Diane McKeone; Rhiannon Walters; Michael D Walsh; Bruce W Young; Jeremy R Jass; Christophe Rosty; Michael Gattas; Elise Pelzer; John L Hopper; Jack Goldblatt; Jill George; Graeme K Suthers; Kerry Phillips; Susan Parry; Sonja Woodall; Julie Arnold; Kathy Tucker; Amanda Muir; Musa Drini; Finlay Macrae; Polly Newcomb; John D Potter; Erika Pavluk; Annika Lindblom; Joanne P Young Journal: Fam Cancer Date: 2011-06 Impact factor: 2.375
Authors: Fernando Bellido; Marta Pineda; Gemma Aiza; Rafael Valdés-Mas; Matilde Navarro; Diana A Puente; Tirso Pons; Sara González; Silvia Iglesias; Esther Darder; Virginia Piñol; José Luís Soto; Alfonso Valencia; Ignacio Blanco; Miguel Urioste; Joan Brunet; Conxi Lázaro; Gabriel Capellá; Xose S Puente; Laura Valle Journal: Genet Med Date: 2015-07-02 Impact factor: 8.822