title: Detection of genetic alterations in hereditary colorectal cancer screening.
abstract: There are two major hereditary colorectal cancer syndromes: Adenomatous Polyposis, secondary to APC germline alterations (FAP, Familial Adenomatous Polyposis) or secondary to MUTYH germline alterations (MAP, MUTYH associated Polyposis), and Lynch syndrome, associated with germline mutations in mismatch repair genes (MLH1, MSH2, MSH6 and PMS2). The elucidation of their genetic basis has depicted an increasingly complex picture that has lead to the implementation of complex diagnostic algorithms that include both tumor profiling and germline analyses. A variety of techniques at the DNA, RNA and protein level are used to screen for molecular alterations both in tumor biopsies (microsatellite instability analysis, mismatch repair protein immunohistochemistry, BRAF-Val600Glu detection and MLH1 promoter hypermethylation analysis) and in the germline (point mutation screening, copy number assessment). Also functional tests are more often used to characterize variants of unknown significance. Methodological issues associated with the techniques analyzed, as well as the algorithms used, are discussed.
authors.affiliation: Translational Research Laboratory and Cancer Genetic Counseling Program, Av. Gran Via de l'Hospitalet 199-203, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Pineda
authors.forename: Sara
authors.initials: S
authors.lastname: González
authors.forename: Conxi
authors.initials: C
authors.lastname: Lázaro
authors.forename: Ignacio
authors.initials: I
authors.lastname: Blanco
authors.forename: Gabriel
authors.initials: G
authors.lastname: Capellá
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics; D016172:DNA Fingerprinting; D004252:DNA Mutational Analysis; D055088:Early Detection of Cancer; D044127:Epigenesis, Genetic; D006801:Humans; D053842:Microsatellite Instability; D009154:Mutation