当前位置： SCI文献检索 > CANCER RESEARCH期刊下所有文献 > Identification of novel gene amplifications in breast cancer and coexistence of gene amplification with an activating mutation of PIK3CA.

Identification of novel gene amplifications in breast cancer and coexistence of gene amplification with an activating mutation of PIK3CA.

Abstract：

:To identify genetic events that characterize cancer progression, we conducted a comprehensive genetic evaluation of 161 primary breast tumors. Similar to the "mountain-and-hill" view of mutations, gene amplification also shows high- and low-frequency alterations in breast cancers. The frequently amplified genes include the well-known oncogenes ERBB2, FGFR1, MYC, CCND1, and PIK3CA, whereas other known oncogenes that are amplified, although less frequently, include CCND2, EGFR, FGFR2, and NOTCH3. More importantly, by honing in on minimally amplified regions containing three or fewer genes, we identified six new amplified genes: POLD3, IRAK4, IRX2, TBL1XR1, ASPH, and BRD4. We found that both the IRX2 and TBL1XR1 proteins showed higher expression in the malignant cell lines MCF10CA1h and MCF10CA1a than in their precursor, MCF10A, a normal immortalized mammary epithelial cell line. To study oncogenic roles of TBL1XR1, we performed knockdown experiments using a short hairpin RNA approach and found that depletion of TBL1XR1 in MCF10CA1h cells resulted in reduction of cell migration and invasion as well as suppression of tumorigenesis in mouse xenografts. Intriguingly, our mutation analysis showed the presence of activation mutations in the PIK3CA gene in a subset of tumors that also had DNA copy number increases in the PIK3CA locus, suggesting an additive effect of coexisting activating amino acid substitution and dosage increase from amplification. Our gene amplification and somatic mutation analysis of breast primary tumors provides a coherent picture of genetic events, both corroborating and novel, offering insight into the genetic underpinnings of breast cancer progression.

journal_name

Cancer Res

journal_title

Cancer research

authors

Kadota M,Sato M,Duncan B,Ooshima A,Yang HH,Diaz-Meyer N,Gere S,Kageyama S,Fukuoka J,Nagata T,Tsukada K,Dunn BK,Wakefield LM,Lee MP

doi

10.1158/0008-5472.CAN-09-0064

subject

Has Abstract

pub_date

2009-09-15 00:00:00

pages

7357-65

issue

eissn

0008-5472

issn

1538-7445

pii

0008-5472.CAN-09-0064

journal_volume

pub_type

杂志文章

在线工具

Identification of novel gene amplifications in breast cancer and coexistence of gene amplification with an activating mutation of PIK3CA.