Open AccessShort somatic alterations at the site of copy number variation in breast cancer
Author(s) -
Murakami Fumi,
Tsuboi Yumi,
Takahashi Yuka,
Horimoto Yoshiya,
Mogushi Kaoru,
Ito Takeshi,
Emi Mitsuru,
Matsubara Daisuke,
Shibata Tatsuhiro,
Saito Mitsue,
Murakami Yoshinori
Publication year - 2021
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14630
Subject(s) - copy number variation , somatic cell , biology , comparative genomic hybridization , breast cancer , gene , estrogen receptor , gene dosage , copy number analysis , cancer , cancer research , genetics , microbiology and biotechnology , genome , gene expression
Copy number variation (CNV) is a polymorphism in the human genome involving DNA fragments larger than 1 kb. Copy number variation sites provide hotspots of somatic alterations in cancers. Herein, we examined somatic alterations at sites of CNV in DNA from 20 invasive breast cancers using a Comparative Genomic Hybridization array specifically designed to detect the genome‐wide CNV status of approximately 412 000 sites. Somatic copy number alterations (CNAs) were detected in 39.9% of the CNV probes examined. The most frequently altered regions were gains of 1q21‐22 (90%), 8q21‐24 (85%), 1q44 (85%), and 3q11 (85%) or losses of 16q22‐24 (80%). Gene ontology analyses of genes within the CNA fragments revealed that cascades related to transcription and RNA metabolism correlated significantly with human epidermal growth factor receptor 2 positivity and menopausal status. Thirteen of 20 tumors showed CNAs in more than 35% of sites examined and a high prevalence of CNAs correlated significantly with estrogen receptor (ER) negativity, higher nuclear grade (NG), and higher Ki‐67 labeling index. Finally, when CNA fragments were categorized according to their size, CNAs smaller than 10 kb correlated significantly with ER positivity and lower NG, whereas CNAs exceeding 10 Mb correlated with higher NG, ER negativity, and a higher Ki‐67 labeling index. Most of these findings were confirmed or supported by quantitative PCR of representative DNA fragments in 72 additional breast cancers. These results suggest that most CNAs are caused by gain or loss of large chromosomal fragments and correlate with NG and several malignant features, whereas solitary CNAs of less than 10 kb could be involved in ER‐positive breast carcinogenesis.