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

• Published in: Oncogene Vol. 27; no. 20; pp. 2929 - 2933
• Main Authors: Schwab, R, Bussolari, R, Corvetta, D, Chayka, O, Santilli, G, Kwok, J M-M, Amorotti, G F, Tonini, G P, Iacoviello, L, Bertorelle, R, Menin, C, Hubank, M, Calabretta, B, Sala, A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2008; Nature Publishing; Nature Publishing Group
• Subjects: Alleles; Apoptosis; B-myb gene; Biological and medical sciences; Cancer; Cell Biology; Cell Cycle Proteins - genetics; Cell Cycle Proteins - physiology; Cell Line; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Colorectal cancer; Control; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Gene expression; Gene regulation; Genes, myb; Genetic aspects; Genetic Variation; Human Genetics; Humans; Internal Medicine; Isoforms; Medical sciences; Medicine; Medicine & Public Health; Molecular and cellular biology; Molecular genetics; MYB gene; MYB protein; Neoplasms - genetics; Neoplasms - prevention & control; Neuroblastoma; Oncogenes; Oncology; Physiological aspects; Polymorphism; Polymorphism, Genetic; Population genetics; Protein Isoforms - genetics; Proto-Oncogene Proteins c-myb - genetics; Proto-Oncogene Proteins c-myb - isolation & purification; Proto-oncogenes; Risk Factors; short-communication; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Trans-Activators - genetics; Trans-Activators - physiology; Transcription. Transcription factor. Splicing. Rna processing; Tumor cell lines; Tumors; United Kingdom; neuroblastoma; leukaemia; apoptosis; transcription; colon cancer; Nervous system diseases; Transcription; Leukemia; Risk; Malignant hemopathy; Neuroblastoma; Malignant tumor; Carcinogenesis; Colonic disease; Variant; Colon cancer; C-Onc gene; Digestive diseases; Intestinal disease; Isolation; Autonomic neuropathy; Transcription factor; Protooncogene; Cancer; Apoptosis; Polymorphism
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1210947

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.