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Differential copy number aberrations in novel candidate genes associated with progression from in situ to invasive ductal carcinoma of the breast.

Publication ,  Journal Article
Liao, S; Desouki, MM; Gaile, DP; Shepherd, L; Nowak, NJ; Conroy, J; Barry, WT; Geradts, J
Published in: Genes Chromosomes Cancer
December 2012

Only a minority of intraductal carcinomas of the breast give rise to stromally invasive disease. We microdissected 206 paraffin blocks representing 116 different cases of low-grade ductal carcinoma in situ (DCIS). Fifty-five were pure DCIS (PD) cases without progression to invasive carcinoma. Sixty-one cases had a small invasive component. DNA was extracted from microdissected sections and hybridized to high-density bacterial artificial chromosome arrays. Array comparative genomic hybridization analysis of 118 hybridized DNA samples yielded data on 69 samples that were suitable for further statistical analysis. This cohort included 20 pure DCIS cases, 25 mixed DCIS (MD), and 24 mixed invasive carcinoma samples. PD cases had a higher frequency of DNA copy number changes than MD cases, and the latter had similar DNA profiles compared to paired invasive carcinomas. Copy number changes on 13 chromosomal arms occurred at different rates in PD versus MD lesions. Eight of 19 candidate genes residing at those loci were confirmed to have differential copy number changes by quantitative PCR. NCOR2/SMRT and NR4A1 (both on 12q), DYNLRB2 (16q), CELSR1, UPK3A, and ST13 (all on 22q) were more frequently amplified in PD. Moreover, NCOR2, NR4A1, and DYNLRB2 showed more frequent copy number losses in MD. GRAP2 (22q) was more often amplified in MD, whereas TAF1C (16q) was more commonly deleted in PD. A multigene model comprising these candidate genes discriminated between PD and MD lesions with high accuracy. These findings suggest that the propensity to invade the stroma may be encoded in the genome of intraductal carcinomas.

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Published In

Genes Chromosomes Cancer

DOI

EISSN

1098-2264

Publication Date

December 2012

Volume

51

Issue

12

Start / End Page

1067 / 1078

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • Humans
  • Female
  • Disease Progression
  • DNA Copy Number Variations
  • Comparative Genomic Hybridization
  • Carcinoma, Intraductal, Noninfiltrating
  • Carcinoma, Ductal, Breast
  • Breast Neoplasms
  • Breast
 

Citation

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Liao, S., Desouki, M. M., Gaile, D. P., Shepherd, L., Nowak, N. J., Conroy, J., … Geradts, J. (2012). Differential copy number aberrations in novel candidate genes associated with progression from in situ to invasive ductal carcinoma of the breast. Genes Chromosomes Cancer, 51(12), 1067–1078. https://doi.org/10.1002/gcc.21991
Liao, Shaoxi, Mohamed M. Desouki, Daniel P. Gaile, Lori Shepherd, Norma J. Nowak, Jeffrey Conroy, William T. Barry, and Joseph Geradts. “Differential copy number aberrations in novel candidate genes associated with progression from in situ to invasive ductal carcinoma of the breast.Genes Chromosomes Cancer 51, no. 12 (December 2012): 1067–78. https://doi.org/10.1002/gcc.21991.
Liao S, Desouki MM, Gaile DP, Shepherd L, Nowak NJ, Conroy J, et al. Differential copy number aberrations in novel candidate genes associated with progression from in situ to invasive ductal carcinoma of the breast. Genes Chromosomes Cancer. 2012 Dec;51(12):1067–78.
Liao, Shaoxi, et al. “Differential copy number aberrations in novel candidate genes associated with progression from in situ to invasive ductal carcinoma of the breast.Genes Chromosomes Cancer, vol. 51, no. 12, Dec. 2012, pp. 1067–78. Pubmed, doi:10.1002/gcc.21991.
Liao S, Desouki MM, Gaile DP, Shepherd L, Nowak NJ, Conroy J, Barry WT, Geradts J. Differential copy number aberrations in novel candidate genes associated with progression from in situ to invasive ductal carcinoma of the breast. Genes Chromosomes Cancer. 2012 Dec;51(12):1067–1078.
Journal cover image

Published In

Genes Chromosomes Cancer

DOI

EISSN

1098-2264

Publication Date

December 2012

Volume

51

Issue

12

Start / End Page

1067 / 1078

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • Humans
  • Female
  • Disease Progression
  • DNA Copy Number Variations
  • Comparative Genomic Hybridization
  • Carcinoma, Intraductal, Noninfiltrating
  • Carcinoma, Ductal, Breast
  • Breast Neoplasms
  • Breast