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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\u2010wide CNV status of approximately 412\u00a0000 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\u201022 (90%), 8q21\u201024 (85%), 1q44 (85%), and 3q11 (85%) or losses of 16q22\u201024 (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\u201067 labeling index. Finally, when CNA fragments were categorized according to their size, CNAs smaller than 10\u00a0kb correlated significantly with ER positivity and lower NG, whereas CNAs exceeding 10\u00a0Mb correlated with higher NG, ER negativity, and a higher Ki\u201067 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\u00a0kb could be involved in ER\u2010positive breast carcinogenesis.<\/jats:p>","DOI":"10.1111\/cas.14630","type":"journal-article","created":{"date-parts":[[2020,8,29]],"date-time":"2020-08-29T08:38:53Z","timestamp":1598690333000},"page":"444-453","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Short somatic alterations at the site of copy number variation in breast cancer"],"prefix":"10.1111","volume":"112","author":[{"given":"Fumi","family":"Murakami","sequence":"first","affiliation":[{"name":"Division of Molecular Pathology The Institute of Medical Science, The University of Tokyo Tokyo Japan"},{"name":"Department of Breast Oncology Juntendo University Tokyo Japan"},{"name":"Juntendo University Graduate School of Medicine Tokyo 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