Short somatic alterations at the site of copy number variation in breast cancer.
Short somatic alterations at the site of copy number variation in breast cancer.
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DOI：
10.1111/cas.14630
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发表时间：
2021-01
期刊：
影响因子：
5.7
通讯作者：
Murakami Y
中科院分区：
文献类型：
--
作者：
Murakami F;Tsuboi Y;Takahashi Y;Horimoto Y;Mogushi K;Ito T;Emi M;Matsubara D;Shibata T;Saito M;Murakami Y
拷贝数变异（Copy number variation，CNV）是指人类基因组中大于1 kb的DNA片段的多态性。拷贝数变异位点提供了癌症中体细胞改变的热点。在本文中，我们使用专门设计用于检测约412 000个位点的全基因组CNV状态的比较基因组杂交阵列，检查了20例浸润性乳腺癌DNA中CNV位点的体细胞改变。在39.9%的CNV探针中检测到体细胞拷贝数改变（CNAs）。最常见的改变区域是1 q21 - 22（90%），8 q21 - 24（85%），1 q44（85%）和3q 11（85%）的增加或16 q22 - 24（80%）的丢失。CNA片段内基因的基因本体分析显示，与转录和RNA代谢相关的级联反应与人表皮生长因子受体2阳性和绝经状态显着相关。20例肿瘤中有13例在超过35%的检查部位显示CNA，CNA的高患病率与雌激素受体（ER）阴性、较高的核分级（NG）和较高的Ki-67标记指数显著相关。最后，当CNA片段根据其大小分类时，小于10 kb的CNA与ER阳性和较低的NG显著相关，而超过10 Mb的CNA与较高的NG、ER阴性和较高的Ki-67标记指数相关。这些发现中的大多数都得到了另外72例乳腺癌中代表性DNA片段定量PCR的证实或支持。这些结果表明，大多数CNA是由大的染色体片段的获得或丢失引起的，并与NG和几种恶性特征相关，而小于10 kb的孤立CNA可能参与ER阳性乳腺癌的发生。部分恶性程度较低的乳腺癌涉及拷贝数变异位点的短长度体细胞改变。
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. Short‐length somatic alterations at the site of copy number variation were involved in a portion of breast cancer with a lower grade malignancy.
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影响因子：
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