GATA3 mutations define a unique subtype of luminal-like breast cancer with improved survival
GATA3 mutations define a unique subtype of luminal-like breast cancer with improved survival
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GATA3突变定义了一种独特的管腔样乳腺癌亚型，可提高生存率
DOI：
10.1002/cncr.28566
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发表时间：
2014-05-01
期刊：
影响因子：
6.2
通讯作者：
Shao, Zhi-Ming
中科院分区：
文献类型：
--
作者：
Jiang, Yi-Zhou;Yu, Ke-Da;Shao, Zhi-Ming
GATA 3基因（GATA结合蛋白3）是乳腺癌中最常见的突变基因之一。本研究的目的是确定乳腺癌患者携带GATA 3突变的临床病理特征. METHODS作者检查了GATA 3的体细胞突变状态，并在癌症基因组图谱（TCGA）队列（n = 934）和复旦大学上海肿瘤中心（FUSCC）队列（n = 308）进行生存分析。患者特征，包括年龄;绝经状态;肿瘤偏侧性;肿瘤大小;淋巴结状态;肿瘤分级;分子亚型;辅助放疗、化疗和内分泌治疗;和预后，以及PIK 3CA（磷脂酰肌醇-4，5-二磷酸3-激酶，催化亚基α）和TP 53（肿瘤蛋白p53）突变状态，在8.8%的患者中检测到TSGATA 3突变，TCGA队列中有82例患者（934例患者中的82例），FUSCC队列中有14.9%的患者（308例患者中的46例）。研究发现GATA 3突变与腔样乳腺癌显着相关（TCGA队列中P = 0.002，FUSCC队列中P <0.001），并且与PIK 3CA突变（TCGA队列中P = 0.001，FUSCC队列中P = 0.003）和TP 53突变（两个队列中P <0.001）高度相互排斥。此外，GATA 3突变与整个人群中总生存率的改善相关。（TCGA组P = 0.025，FUSCC组P = 0.043）以及接受辅助内分泌治疗的管腔样疾病患者中。结论SGATA 3突变主要发生在管腔样乳腺癌患者中，具有可识别的临床病理和遗传特征，突出了可能适合有限治疗的乳腺癌患者亚组。Cancer 2014;120：1329-1337. (c)2014年美国癌症协会
BACKGROUNDThe GATA3 gene (GATA-binding protein 3) is one of the most frequently mutated genes in breast cancer. The objective of the current study was to determine the clinicopathologic characteristics of patients with breast cancer harboring GATA3 mutations.METHODSThe authors examined the somatic mutation status of GATA3 and performed survival analysis in The Cancer Genome Atlas (TCGA) cohort (n = 934) and the Fudan University Shanghai Cancer Center (FUSCC) cohort (n = 308). Patient characteristics, including age; menopausal status; tumor laterality; tumor size; lymph node status; tumor grade; molecular subtypes; adjuvant radiotherapy, chemotherapy, and endocrine therapy; and prognosis, together with PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) and TP53 (tumor protein p53) mutation status, were collected.RESULTSGATA3 mutations were detected in 8.8% of patients (82 of 934 patients) in the TCGA cohort and 14.9% of patients (46 of 308 patients) in the FUSCC cohort. GATA3 mutations were found to be significantly associated with luminal-like breast cancer (P = .002 in the TCGA cohort and P < .001 in the FUSCC cohort), and were highly mutually exclusive to PIK3CA mutations (P = .001 in the TCGA cohort and P = .003 in the FUSCC cohort) and TP53 mutations (P < .001 in both cohorts). Furthermore, GATA3 mutations were correlated with improved overall survival in the entire population (P = .025 in the TCGA cohort and P = .043 in the FUSCC cohort) as well as in patients with luminal-like disease who received adjuvant endocrine therapy.CONCLUSIONSGATA3 mutations mainly occur in patients with luminal-like breast cancer and have identifiable clinicopathologic and genetic characteristics, highlighting a subgroup of patients with breast cancer in whom limited therapy may be appropriate. Cancer 2014;120:1329-1337. (c) 2014 American Cancer Society.