Germline mutations in the spindle assembly checkpoint genes BUB1 and BUB3 are infrequent in familial colorectal cancer and polyposis

Germline mutations in BUB1 and BUB3 have been reported to increase the risk of developing colorectal cancer (CRC) at young age, in presence of variegated aneuploidy and reminiscent dysmorphic traits of mosaic variegated aneuploidy syndrome. We performed a mutational analysis of BUB1 and BUB3 in 456...

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Detalhes bibliográficos
Autores: Mur, Pilar, de Voer, Richarda M., Olivera-Salguero, Rubén, Rodriguez Perales, Sandra, Pons, Tirso, Setién, Fernando, Aiza, Gemma, Valdés Mas, Rafael, Bertini, Angelo, Pineda Riu, Marta, Vreede, Lilian, Navarro, Matilde, Iglesias Casals, Sílvia, González, Sara, Brunet, Joan, Valencia, Alfonso, Esteller, Manel, Lázaro García, Conxi, Kops, Geert J. P. L., Urioste, Miguel, Puente, Xose S., Capellá, G. (Gabriel), Valle Velasco, Laura
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2018
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/120947
Acesso em linha:https://hdl.handle.net/2445/120947
Access Level:Acceso aberto
Palavra-chave:Càncer colorectal
Genètica mèdica
Malalties hereditàries
Colorectal cancer
Medical genetics
Genetic diseases
Descrição
Resumo:Germline mutations in BUB1 and BUB3 have been reported to increase the risk of developing colorectal cancer (CRC) at young age, in presence of variegated aneuploidy and reminiscent dysmorphic traits of mosaic variegated aneuploidy syndrome. We performed a mutational analysis of BUB1 and BUB3 in 456 uncharacterized mismatch repair-proficient hereditary non-polyposis CRC families and 88 polyposis cases. Four novel or rare germline variants, one splice-site and three missense, were identified in four families. Neither variegated aneuploidy nor dysmorphic traits were observed in carriers. Evident functional effects in the heterozygous form were observed for c.1965-1G>A, but not for c.2296G>A (p.E766K), in spite of the positive co-segregation in the family. BUB1 c.2473C>T (p.P825S) and BUB3 c.77C>T (p.T26I) remained as variants of uncertain significance. As of today, the rarity of functionally relevant mutations identified in familial and/or early onset series does not support the inclusion of BUB1 and BUB3 testing in routine genetic diagnostics of familial CRC.

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