MYB oncogene amplification in hereditary BRCA1 breast cancer.
Comparative genomic hybridization analysis has demonstrated that breast tumors from BRCA1 and BRCA2 germ-line mutation carriers contain a large number of chromosomal copy number gains and losses. A high regional copy number gain at 6q22-q24 was observed in one BRCA1 tumor, and fluorescence in situ hybridization analysis indicated a strong amplification of the MYB oncogene (15 copies of MYB compared with 1 copy of chromosome 6 centromere). Fluorescence in situ hybridization analysis revealed amplification of MYB in 5 (29%) of 17 BRCA1 breast tumors, whereas none of 8 BRCA2 tumors and 13 breast cancer cell lines, and only 2 of 100 sporadic breast tumors exhibited altered MYB copy numbers. Gene amplification resulted in mRNA overexpression as determined by Northern blot and cDNA microarray analysis, and protein overexpression by immunohistochemical staining. We conclude that MYB amplification is infrequent in sporadic breast cancer but common in breast tumors from BRCA1 mutation carriers, suggesting a role of this cell cycle regulator and transcription factor in the progression of some BRCA1 tumors. However, we cannot rule out the significance of other genes in the 6q22-q24 amplicon.
Kauraniemi
P
P
Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere, Finland.
Hedenfalk
I
I
Persson
K
K
Duggan
D J
DJ
Tanner
M
M
Johannsson
O
O
Olsson
H
H
Trent
J M
JM
Isola
J
J
Borg
A
A
D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005784:Gene Amplification; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D019398:Genes, BRCA1 / Q000235:genetics*; D020570:Genes, myb / Q000235:genetics*; D018095:Germ-Line Mutation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009693:Nucleic Acid Hybridization; D020626:Oncogene Proteins v-myb / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000502:physiology; D011980:Receptors, Progesterone / Q000502:physiology
D018076:DNA, Complementary; D004273:DNA, Neoplasm; D020626:Oncogene Proteins v-myb; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone