X chromosomal abnormalities in basal-like human breast cancer.
Sporadic basal-like cancers (BLC) are a distinct class of human breast cancers that are phenotypically similar to BRCA1-associated cancers. Like BRCA1-deficient tumors, most BLC lack markers of a normal inactive X chromosome (Xi). Duplication of the active X chromosome and loss of Xi characterized almost half of BLC cases tested. Others contained biparental but nonheterochromatinized X chromosomes or gains of X chromosomal DNA. These abnormalities did not lead to a global increase in X chromosome transcription but were associated with overexpression of a small subset of X chromosomal genes. Other, equally aneuploid, but non-BLC rarely displayed these X chromosome abnormalities. These results suggest that X chromosome abnormalities contribute to the pathogenesis of BLC, both inherited and sporadic.
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Andrea L
AL
Richardson
Zhigang C
ZC
Wang
Arcangela
A
De Nicolo
Xin
X
Lu
Myles
M
Brown
Alexander
A
Miron
Xiaodong
X
Liao
J Dirk
JD
Iglehart
David M
DM
Livingston
Shridar
S
Ganesan
D000483:Alleles; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism; D001692:Biological Transport; D015415:Biomarkers; D001943:Breast Neoplasms / Q000235:genetics*; D002467:Cell Nucleus / Q000378:metabolism; D002869:Chromosome Aberrations; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D041321:Chromosomes, Human, X / Q000235:genetics*; D015331:Cohort Studies; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D015870:Gene Expression; D020868:Gene Silencing; D050172:Genes, X-Linked; D006801:Humans; D018295:Neoplasms, Basal Cell / Q000235:genetics*; D062085:RNA, Long Noncoding; D012333:RNA, Messenger / Q000235:genetics; D022661:RNA, Untranslated / Q000235:genetics; D024182:Uniparental Disomy
D019313:BRCA1 Protein; D015415:Biomarkers; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D022661:RNA, Untranslated; C077885:XIST non-coding RNA