Journal Article
. 2012 Oct;7(10).
doi: 10.1371/journal.pone.0046814.

Molecular alterations associated with breast cancer mortality

Laura M Voeghtly 1 Kim Mamula  J Leigh Campbell  Craig D Shriver  Rachel E Ellsworth  
Affiliations
  • PMID: 23056464
  •     34 References
  •     6 citations

Abstract

Background: Breast cancer is a heterogeneous disease and patients with similar pathologies and treatments may have different clinical outcomes. Identification of molecular alterations associated with disease outcome may improve risk assessment and treatments for aggressive breast cancer.

Methods: Allelic imbalance (AI) data was generated for 122 invasive breast tumors with known clinical outcome. Levels and patterns of AI were compared between patients who died of disease (DOD) and those with ≥5 years disease-free survival (DFS) using Student t-test and chi-square analysis with a significance value of P<0.05.

Results: Levels of AI were significantly higher in tumors from the 31 DOD patients (28.6%) compared to the 91 DFS patients (20.1%). AI at chromosomes 7q31, 8p22, 13q14, 17p13.3, 17p13.1 and 22q12.3 was associated with DOD while AI at 16q22-q24 was associated with DFS. After multivariate analysis, AI at chromosome 8p22 remained an independent predictor of breast cancer mortality. The frequency of AI at chromosome 13q14 was significantly higher in patients who died ≥5 years compared to those who died <5 years from diagnosis.

Conclusion: Tumors from DOD compared to DFS patients are marked by increased genomic instability and AI at chromosome 8p22 is significantly associated with breast cancer morality, independent of other clinicopathological factors. AI at chromosome 13q14 was associated with late (>5-years post-diagnosis) mortality but not with death from disease within five years, suggesting that patients with short- and long-term mortality may have distinct genetic diseases.

Gene expression meta-analysis identifies chromosomal regions and candidate genes involved in breast cancer metastasis.
Mads Thomassen, Qihua Tan, Torben A Kruse.
Breast Cancer Res Treat, 2008 Feb 23; 113(2). PMID: 18293085
DLC1 suppresses distant dissemination of human hepatocellular carcinoma cells in nude mice through reduction of RhoA GTPase activity, actin cytoskeletal disruption and down-regulation of genes involved in metastasis.
Xiaoling Zhou, Drazen B Zimonjic, +3 authors, Nicholas C Popescu.
Int J Oncol, 2008 May 24; 32(6). PMID: 18497990    Free PMC article.
Loss of 16q in high grade breast cancer is associated with estrogen receptor status: Evidence for progression in tumors with a luminal phenotype?
Rachael Natrajan, Maryou B K Lambros, +10 authors, Jorge S Reis-Filho.
Genes Chromosomes Cancer, 2009 Jan 22; 48(4). PMID: 19156836
Loss of heterozygosity assay for molecular detection of cancer using energy-transfer primers and capillary array electrophoresis.
I L Medintz, C C Lee, +3 authors, R A Mathies.
Genome Res, 2000 Aug 25; 10(8). PMID: 10958639    Free PMC article.
The RhoGAP protein DLC-1 functions as a metastasis suppressor in breast cancer cells.
Steve Goodison, Jing Yuan, +4 authors, Virginia Urquidi.
Cancer Res, 2005 Jul 19; 65(14). PMID: 16024604    Free PMC article.
Laser capture microdissection of paraffin-embedded tissues.
D L Ellsworth, C D Shriver, +2 authors, R I Somiari.
Biotechniques, 2003 Jan 28; 34(1). PMID: 12545536
Molecular portraits of human breast tumours.
C M Perou, T Sørlie, +15 authors, D Botstein.
Nature, 2000 Aug 30; 406(6797). PMID: 10963602
Highly Cited.
Gene expression profiling predicts clinical outcome of breast cancer.
Laura J van 't Veer, Hongyue Dai, +13 authors, Stephen H Friend.
Nature, 2002 Feb 02; 415(6871). PMID: 11823860
Highly Cited.
High-throughput loss of heterozygosity mapping in 26 commonly deleted regions in breast cancer.
Rachel E Ellsworth, Darrell L Ellsworth, +3 authors, Craig D Shriver.
Cancer Epidemiol Biomarkers Prev, 2003 Sep 25; 12(9). PMID: 14504204
Breast cancer in young women (< or = 35 years): Genomic aberrations detected by comparative genomic hybridization.
Susanne Weber-Mangal, Hans-Peter Sinn, +7 authors, Anna Jauch.
Int J Cancer, 2003 Oct 02; 107(4). PMID: 14520696
Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up.
C W Elston, I O Ellis.
Histopathology, 1991 Nov 01; 19(5). PMID: 1757079
Highly Cited.
Genomic distance entrained clustering and regression modelling highlights interacting genomic regions contributing to proliferation in breast cancer.
Tim J Dexter, David Sims, +4 authors, Marketa Zvelebil.
BMC Syst Biol, 2010 Sep 10; 4. PMID: 20825665    Free PMC article.
Amplification of HER2 is a marker for global genomic instability.
Rachel E Ellsworth, Darrell L Ellsworth, +4 authors, Craig D Shriver.
BMC Cancer, 2008 Oct 16; 8. PMID: 18854030    Free PMC article.
Prognostic and predictive value of 16p12.1 and 16q22.1 copy number changes in human breast cancer.
Tricia E Downing, Maja H Oktay, Melissa J Fazzari, Cristina Montagna.
Cancer Genet Cytogenet, 2010 Mar 23; 198(1). PMID: 20303015
"Good Old" clinical markers have similar power in breast cancer prognosis as microarray gene expression profilers.
Patrik Edén, Cecilia Ritz, +2 authors, Carsten Peterson.
Eur J Cancer, 2004 Aug 04; 40(12). PMID: 15288284
Selective genomic copy number imbalances and probability of recurrence in early-stage breast cancer.
Patricia A Thompson, Abenaa M Brewster, +12 authors, Melissa L Bondy.
PLoS One, 2011 Aug 23; 6(8). PMID: 21858162    Free PMC article.
Correlation of Allelic Loss with Poor Postoperative Survival in Breast Cancer.
Emi, Utada, +10 authors, Nakamura.
Breast Cancer, 2000 Nov 25; 6(4). PMID: 11091742
Molecular changes in primary breast tumors and the Nottingham Histologic Score.
Rachel E Ellsworth, Jeffrey A Hooke, +2 authors, Craig D Shriver.
Pathol Oncol Res, 2009 Feb 06; 15(4). PMID: 19194786
DLC-1 gene inhibits human breast cancer cell growth and in vivo tumorigenicity.
Bao-Zhu Yuan, Xiaoling Zhou, +5 authors, Nicholas C Popescu.
Oncogene, 2003 Jan 25; 22(3). PMID: 12545165
Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer.
Soonmyung Paik, Gong Tang, +11 authors, Norman Wolmark.
J Clin Oncol, 2006 May 25; 24(23). PMID: 16720680
Highly Cited.
Localization of a tumor suppressor gene associated with the progression of human breast carcinoma within a 1-cM interval of 8p22-p23.1.
T Yokota, M Yoshimoto, +4 authors, M Emi.
Cancer, 1999 Feb 19; 85(2). PMID: 10023714
Genome-wide analysis identifies 16q deletion associated with survival, molecular subtypes, mRNA expression, and germline haplotypes in breast cancer patients.
Silje H Nordgard, Fredrik E Johansen, +5 authors, Vessela N Kristensen.
Genes Chromosomes Cancer, 2008 Apr 10; 47(8). PMID: 18398821
A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer.
Soonmyung Paik, Steven Shak, +12 authors, Norman Wolmark.
N Engl J Med, 2004 Dec 14; 351(27). PMID: 15591335
Highly Cited.
Patterns of chromosomal imbalances defines subgroups of breast cancer with distinct clinical features and prognosis. A study of 305 tumors by comparative genomic hybridization.
Karin Rennstam, Minna Ahlstedt-Soini, +6 authors, Jorma Isola.
Cancer Res, 2003 Dec 26; 63(24). PMID: 14695203
Cloning, characterization, and chromosomal localization of a gene frequently deleted in human liver cancer (DLC-1) homologous to rat RhoGAP.
B Z Yuan, M J Miller, +3 authors, N C Popescu.
Cancer Res, 1998 May 30; 58(10). PMID: 9605766
Highly Cited.
Improvement of best practice in early breast cancer: actionable surgeon and hospital factors.
Marjan Gort, Manda Broekhuis, Renée Otter, Niek S Klazinga.
Breast Cancer Res Treat, 2006 Oct 10; 102(2). PMID: 17028985
RB1CC1 together with RB1 and p53 predicts long-term survival in Japanese breast cancer patients.
Tokuhiro Chano, Kaichiro Ikebuchi, +14 authors, Hidetoshi Okabe.
PLoS One, 2011 Jan 05; 5(12). PMID: 21203526    Free PMC article.
DNA sequence losses on chromosomes 11p and 18q are associated with clinical outcome in lymph node-negative ductal breast cancer.
Athanassios Dellas, Joachim Torhorst, +2 authors, Holger Moch.
Clin Cancer Res, 2002 May 15; 8(5). PMID: 12006540
Histological grading and prognosis in breast cancer; a study of 1409 cases of which 359 have been followed for 15 years.
H J BLOOM, W W RICHARDSON.
Br J Cancer, 1957 Sep 01; 11(3). PMID: 13499785    Free PMC article.
Highly Cited.
Allelic losses of loci at 3p25.1, 8p22, 13q12, 17p13.3, and 22q13 correlate with postoperative recurrence in breast cancer.
A Hirano, M Emi, +8 authors, Y Nakamura.
Clin Cancer Res, 2001 Apr 20; 7(4). PMID: 11309336
Correlation of levels and patterns of genomic instability with histological grading of invasive breast tumors.
Rachel E Ellsworth, Jeffrey A Hooke, +4 authors, Craig D Shriver.
Breast Cancer Res Treat, 2007 Mar 14; 107(2). PMID: 17351743
Loss of heterozygosity on chromosome 7q and aggressive primary breast cancer.
I Bièche, M H Champème, +3 authors, R Lidereau.
Lancet, 1992 Jan 18; 339(8786). PMID: 1346009
Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications.
T Sørlie, C M Perou, +14 authors, A L Børresen-Dale.
Proc Natl Acad Sci U S A, 2001 Sep 13; 98(19). PMID: 11553815    Free PMC article.
Highly Cited.
Allelic loss at the 8p22 region as a prognostic factor in large and estrogen receptor negative breast carcinomas.
Y Utada, S Haga, +4 authors, M Emi.
Cancer, 2000 Mar 16; 88(6). PMID: 10717624
Deleted in liver cancer-1 (DLC1): an emerging metastasis suppressor gene.
Nicholas C Popescu, Steve Goodison.
Mol Diagn Ther, 2014 Feb 13; 18(3). PMID: 24519699    Free PMC article.
Review.
Role of the staphylococcal nuclease and tudor domain containing 1 in oncogenesis (review).
Nidhi Jariwala, Devaraja Rajasekaran, +6 authors, Devanand Sarkar.
Int J Oncol, 2014 Nov 19; 46(2). PMID: 25405367    Free PMC article.
Review.
Mosaic 13q14 deletions in peripheral leukocytes of non-hematologic cancer cases and healthy controls.
Mitchell J Machiela, Weiyin Zhou, +6 authors, Stephen J Chanock.
J Hum Genet, 2016 Jan 15; 61(5). PMID: 26763882    Free PMC article.
OVCA1 expression and its correlation with the expression levels of cyclin D1 and p16 in cervical cancer and intraepithelial neoplasia.
Rui Tong, Qing Yang, +2 authors, Bing Jiang.
Oncol Lett, 2017 May 20; 13(5). PMID: 28521400    Free PMC article.
MicroRNA-132 induces temozolomide resistance and promotes the formation of cancer stem cell phenotypes by targeting tumor suppressor candidate 3 in glioblastoma.
Zhen-Xiu Cheng, Wen-Bo Yin, Zhong-Yu Wang.
Int J Mol Med, 2017 Sep 14; 40(5). PMID: 28901390    Free PMC article.
Phosphorylation of human TRM9L integrates multiple stress-signaling pathways for tumor growth suppression.
Chen Gu, Jillian Ramos, +3 authors, Thomas J Begley.
Sci Adv, 2018 Jul 17; 4(7). PMID: 30009260    Free PMC article.