Breast cancer and aneusomy 17: implications for carcinogenesis and therapeutic response.
Abnormalities of chromosome 17, recognised over two decades ago to be important in tumorigenesis, often occur in breast cancer. Changes of specific loci on chromosome 17 including ERBB2 amplification, P53 loss, BRCA1 loss, and TOP2A amplification or deletion are known to have important roles in breast-cancer pathophysiology. Numerical aberrations of chromosome 17 are linked to breast-cancer initiation and progression, and possibly to treatment response. However, the clinical importance of chromosome 17 anomalies, in particular the effect on ERBB2 protein expression, is unknown. Reports are conflicting regarding the association of copy gain of chromosome 17 (polysomy 17) with strong ERBB2 protein expression in the absence of true ERBB2 gene amplification. Copy-number anomalies in chromosome 17 seem to be common in tumours that show discrepant ERBB2 expression and in tumours with discordant ERBB2-protein and ERBB2 gene copy number measurements. The mechanisms of ERBB2 dosage changes-gene amplification versus chromosome gain and loss-probably differ in primary and metastatic disease; however, a correction for chromosome 17 copy-number is necessary to completely distinguish between these mechanisms. A better understanding of how polysomy 17 affects gene-copy number and protein expression will help to select patients who will respond to therapies targeting ERBB2 and other protein products of chromosome 17 loci.
Reinholz
Monica M
MM
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Bruzek
Amy K
AK
Visscher
Daniel W
DW
Lingle
Wilma L
WL
Schroeder
Matthew J
MJ
Perez
Edith A
EA
Jenkins
Robert B
RB
D000782:Aneuploidy; D000951:Antigens, Neoplasm / Q000235:genetics; D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics* / Q000628:therapy; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2; D016158:Genes, p53; D006801:Humans; D000075223:Poly-ADP-Ribose Binding Proteins; D011379:Prognosis
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human