Genome-wide copy number alterations in subtypes of invasive breast cancers in young white and African American women.
Genomic copy number alterations (CNA) are common in breast cancer. Identifying characteristic CNAs associated with specific breast cancer subtypes is a critical step in defining potential mechanisms of disease initiation and progression. We used genome-wide array comparative genomic hybridization to identify distinctive CNAs in breast cancer subtypes from 259 young (diagnosed with breast cancer at <55 years) African American (AA) and Caucasian American (CA) women originally enrolled in a larger population-based study. We compared the average frequency of CNAs across the whole genome for each breast tumor subtype and found that estrogen receptor (ER)-negative tumors had a higher average frequency of genome-wide gain (P < 0.0001) and loss (P = 0.02) compared to ER-positive tumors. Triple-negative (TN) tumors had a higher average frequency of genome-wide gain (P < 0.0001) and loss (P = 0.003) than non-TN tumors. No significant difference in CNA frequency was observed between HER2-positive and -negative tumors. We also identified previously unreported recurrent CNAs (frequency >40%) for TN breast tumors at 10q, 11p, 11q, 16q, 20p, and 20q. In addition, we report CNAs that differ in frequency between TN breast tumors of AA and CA women. This is of particular relevance because TN breast cancer is associated with higher mortality and young AA women have higher rates of TN breast tumors compared to CA women. These data support the possibility that higher overall frequency of genomic alteration events as well as specific focal CNAs in TN breast tumors might contribute in part to the poor breast cancer prognosis for young AA women.
Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N C1-015, Seattle, WA 98109, USA.
Lenora W M
LW
Loo
Yinghui
Y
Wang
Erin M
EM
Flynn
Mary Jo
MJ
Lund
Erin J Aiello
EJ
Bowles
Diana S M
DS
Buist
Jonathan M
JM
Liff
Elaine W
EW
Flagg
Ralph J
RJ
Coates
J William
JW
Eley
Li
L
Hsu
Peggy L
PL
Porter
D000328:Adult; D001741:Black or African American / Q000235:genetics; D000367:Age Factors; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D016000:Cluster Analysis; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D006801:Humans; D008875:Middle Aged; D044465:White People / Q000235:genetics; D055815:Young Adult
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