The B-MYB proto-oncogene is a transcription factor belonging to the MYB family that is frequently overexpressed or amplified in different types of human malignancies. While it is suspected that B-MYB plays a role in human cancer, there is still no direct evidence of its causative role. Looking for mutations of the B-MYB gene in human cell lines and primary cancer samples, we frequently isolated two nonsynonymous B-MYB polymorphic variants (rs2070235 and rs11556379). Compared to the wild-type protein, the B-MYB isoforms display altered conformation, impaired regulation of target genes and decreased antiapoptotic activity, suggesting that they are hypomorphic variants of the major allele. Importantly, the B-MYB polymorphisms are common; rs2070235 and rs11556379 are found, depending on the ethnic background, in 10-50% of human subjects. We postulated that, if B-MYB activity is important for transformation, the presence of common, hypomorphic variants might modify cancer risk. Indeed, the B-MYB polymorphisms are underrepresented in 419 cancer patients compared to 230 controls (odds ratio 0.53; (95%) confidence interval 0.385-0.755; P=0.001). This data imply that a large fraction of the human population is carrier of B-MYB alleles that might be associated with a reduced risk of developing neoplastic disease.

Isolation and functional assessment of common, polymorphic variants of the B-MYB proto-oncogene associated with a reduced cancer risk / Schwab, R; Bussolari, Rita; Corvetta, D; Chayka, O; Santilli, G; Kwok, Jm; Ferrari, Giovanna; Tonini, Gp; Iacoviello, L; Bertorelle, R; Menin, C; Hubank, M; Calabretta, Bruno; Sala, A.. - In: ONCOGENE. - ISSN 0950-9232. - STAMPA. - 27:(2008), pp. 2929-2933.

Isolation and functional assessment of common, polymorphic variants of the B-MYB proto-oncogene associated with a reduced cancer risk.

BUSSOLARI, Rita;FERRARI, Giovanna;CALABRETTA, Bruno;
2008

Abstract

The B-MYB proto-oncogene is a transcription factor belonging to the MYB family that is frequently overexpressed or amplified in different types of human malignancies. While it is suspected that B-MYB plays a role in human cancer, there is still no direct evidence of its causative role. Looking for mutations of the B-MYB gene in human cell lines and primary cancer samples, we frequently isolated two nonsynonymous B-MYB polymorphic variants (rs2070235 and rs11556379). Compared to the wild-type protein, the B-MYB isoforms display altered conformation, impaired regulation of target genes and decreased antiapoptotic activity, suggesting that they are hypomorphic variants of the major allele. Importantly, the B-MYB polymorphisms are common; rs2070235 and rs11556379 are found, depending on the ethnic background, in 10-50% of human subjects. We postulated that, if B-MYB activity is important for transformation, the presence of common, hypomorphic variants might modify cancer risk. Indeed, the B-MYB polymorphisms are underrepresented in 419 cancer patients compared to 230 controls (odds ratio 0.53; (95%) confidence interval 0.385-0.755; P=0.001). This data imply that a large fraction of the human population is carrier of B-MYB alleles that might be associated with a reduced risk of developing neoplastic disease.
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Isolation and functional assessment of common, polymorphic variants of the B-MYB proto-oncogene associated with a reduced cancer risk / Schwab, R; Bussolari, Rita; Corvetta, D; Chayka, O; Santilli, G; Kwok, Jm; Ferrari, Giovanna; Tonini, Gp; Iacoviello, L; Bertorelle, R; Menin, C; Hubank, M; Calabretta, Bruno; Sala, A.. - In: ONCOGENE. - ISSN 0950-9232. - STAMPA. - 27:(2008), pp. 2929-2933.
Schwab, R; Bussolari, Rita; Corvetta, D; Chayka, O; Santilli, G; Kwok, Jm; Ferrari, Giovanna; Tonini, Gp; Iacoviello, L; Bertorelle, R; Menin, C; Hubank, M; Calabretta, Bruno; Sala, A.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/595112
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