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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Bibliographic Details
Authors: 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, 1968-, Lázaro García, Conxi, Kops, Geert J. P. L., Urioste, Miguel, Puente, Xose S., Capellá, G. (Gabriel), Valle Velasco, Laura
Format: article
Status:Published version
Publication Date:2018
Country:España
Institution:Universidad de Barcelona
Repository:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/120947
Online Access:https://hdl.handle.net/2445/120947
Access Level:Open access
Keyword:Càncer colorectal
Genètica mèdica
Malalties hereditàries
Colorectal cancer
Medical genetics
Genetic diseases
Description
Summary: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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