TY - JOUR
T1 - DNA defects, epigenetics, and gene expression in cancer-adjacent breast
T2 - A study from the cancer genome atlas
AU - Troester, Melissa A.
AU - Hoadley, Katherine A.
AU - D’arcy, Monica
AU - Cherniack, Andrew D.
AU - Stewart, Chip
AU - Koboldt, Daniel C.
AU - Robertson, A. Gordon
AU - Mahurkar, Swapna
AU - Shen, Hui
AU - Wilkerson, Matthew D.
AU - Sandhu, Rupninder
AU - Johnson, Nicole B.
AU - Allison, Kimberly H.
AU - Beck, Andrew H.
AU - Yau, Christina
AU - Bowen, Jay
AU - Sheth, Margi
AU - Hwang, E. Shelley
AU - Perou, Charles M.
AU - Laird, Peter W.
AU - Ding, Li
AU - Benz, Christopher C.
N1 - Publisher Copyright:
© 2016 Breast Cancer Research Foundation/Macmillan Publishers Limited.
PY - 2016/12/14
Y1 - 2016/12/14
N2 - Recurrence rates after breast-conserving therapy may depend on genomic characteristics of cancer-adjacent, benign-appearing tissue. Studies have not evaluated recurrence in association with multiple genomic characteristics of cancer-adjacent breast tissue. To estimate the prevalence of DNA defects and RNA expression subtypes in cancer-adjacent, benign-appearing breast tissue at least 2 cm from the tumor margin, cancer-adjacent, pathologically well-characterized, benign-appearing breast tissue specimens from The Cancer Genome Atlas project were analyzed for DNA sequence, copy-number variation, DNA methylation, messenger RNA (mRNA) sequence, and mRNA/microRNA expression. Additional samples were also analyzed by at least one of these genomic data types and associations between genomic characteristics of normal tissue and overall survival were assessed. Approximately 40% of cancer-adjacent, benign-appearing tissues harbored genomic defects in DNA copy number, sequence, methylation, or in RNA sequence, although these defects did not significantly predict 10-year overall survival. Two mRNA/microRNA expression phenotypes were observed, including an active mRNA subtype that was identified in 40% of samples. Controlling for tumor characteristics and the presence of genomic defects, this active subtype was associated with significantly worse 10-year survival among estrogen receptor (ER)-positive cases. This multi-platform analysis of breast cancer-adjacent samples produced genomic findings consistent with current surgical margin guidelines, and provides evidence that extratumoral RNA expression patterns in cancer-adjacent tissue predict overall survival among patients with ER-positive disease.
AB - Recurrence rates after breast-conserving therapy may depend on genomic characteristics of cancer-adjacent, benign-appearing tissue. Studies have not evaluated recurrence in association with multiple genomic characteristics of cancer-adjacent breast tissue. To estimate the prevalence of DNA defects and RNA expression subtypes in cancer-adjacent, benign-appearing breast tissue at least 2 cm from the tumor margin, cancer-adjacent, pathologically well-characterized, benign-appearing breast tissue specimens from The Cancer Genome Atlas project were analyzed for DNA sequence, copy-number variation, DNA methylation, messenger RNA (mRNA) sequence, and mRNA/microRNA expression. Additional samples were also analyzed by at least one of these genomic data types and associations between genomic characteristics of normal tissue and overall survival were assessed. Approximately 40% of cancer-adjacent, benign-appearing tissues harbored genomic defects in DNA copy number, sequence, methylation, or in RNA sequence, although these defects did not significantly predict 10-year overall survival. Two mRNA/microRNA expression phenotypes were observed, including an active mRNA subtype that was identified in 40% of samples. Controlling for tumor characteristics and the presence of genomic defects, this active subtype was associated with significantly worse 10-year survival among estrogen receptor (ER)-positive cases. This multi-platform analysis of breast cancer-adjacent samples produced genomic findings consistent with current surgical margin guidelines, and provides evidence that extratumoral RNA expression patterns in cancer-adjacent tissue predict overall survival among patients with ER-positive disease.
UR - http://www.scopus.com/inward/record.url?scp=84995575019&partnerID=8YFLogxK
U2 - 10.1038/npjbcancer.2016.7
DO - 10.1038/npjbcancer.2016.7
M3 - Article
AN - SCOPUS:84995575019
SN - 2374-4677
VL - 2
JO - npj Breast Cancer
JF - npj Breast Cancer
IS - 1
M1 - 16007
ER -