Patterns of chromosomal alterations in breast ductal carcinoma in situ.
OBJECTIVE
Ductal carcinoma in situ (DCIS) is thought to be a nonobligate precursor of invasive cancer. Genomic changes specific to pure DCIS versus invasive cancer, as well as alterations unique to individual DCIS subtypes, have not been fully defined.


METHODS
Chromosomal copy number alterations were examined by comparative genomic hybridization in 34 cases of pure DCIS and compared with 12 cases of paired synchronous DCIS and invasive ductal cancer, as well as to 146 additional cases of invasive breast cancer of ductal or lobular histology. Genomic differences between high-grade and low/intermediate-grade DCIS, as well as between pure DCIS and invasive cancer, were identified.


RESULTS
Pure DCIS showed almost the same degree of chromosomal instability as invasive ductal cancers. A higher proportion of low/intermediate-grade versus high-grade DCIS had loss of 16q (65 versus 12%, respectively; P = 0.002). When compared with lower grade DCIS, high-grade DCIS exhibited more frequent gain of 17q (65 versus 41%; P = 0.15) and higher frequency loss of 8p (77 versus 41%; P = 0.04). Chromosomal alterations in those cases with synchronous DCIS and invasive ductal cancer showed a high degree of shared changes within the two components.


CONCLUSIONS
DCIS is genetically advanced, showing a similar degree of chromosomal alterations as invasive ductal cancer. The pattern of alterations differed between high- and low/intermediate-grade DCIS, supporting a model in which different histological grades of DCIS are associated with distinct genomic changes. These regions of chromosomal alterations may be potential targets for treatment and/or markers of prognosis.
Hwang
E Shelley
ES
Department of Surgery, University of California San Francisco, San Francisco, California 94115, USA. shelley.hwang@ucsfmedctr.org
DeVries
Sandy
S
Chew
Karen L
KL
Moore
Dan H
DH
Kerlikowske
Karla
K
Thor
Ann
A
Ljung
Britt-Marie
BM
Waldman
Frederic M
FM
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics*; D043171:Chromosomal Instability; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002875:Chromosomes / Q000648:ultrastructure*; D004247:DNA / Q000235:genetics; D005260:Female; D006801:Humans; D008875:Middle Aged; D008957:Models, Genetic; D009361:Neoplasm Invasiveness; D009693:Nucleic Acid Hybridization; D015995:Prevalence; D011379:Prognosis; D013997:Time Factors
D004247:DNA