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桓兴医讯 17个乳腺癌易感基因的遗传突变在一个大的未选择乳腺癌
文章来源:北京市朝阳区桓兴肿瘤医院 点击数: 发布时间:2014-12-10 08:14
《临床肿瘤杂志》2014年12月1日在线先发
17个乳腺癌易感基因的遗传突变在一个大的未选择乳腺癌家族史的三阴性乳腺癌队列
目的:
DNA测序的最新进展已导致了乳腺癌易感基因的发展,对于患者的生殖细胞进行基因测序。我们评估了17个易感基因的突变频率,包括BRCA1and BRCA2,在一个大的病人队列里,未选择乳腺癌或者卵巢癌家族史的三阴性乳腺癌(TNBC)患者,在那些患者里决定生殖细胞基因检测。
病人和方法:
未选择乳腺癌或者卵巢癌家族史的三阴性乳腺癌患者(N =1824)通过12个研究被招募,并且对生殖细胞DNA进行测序以确定突变。
结果:
所有的患者中有害的突变在14.6%。在这些中,11.2%有BRCA1(8.5%)和BRCA2(2.7%)基因突变。15个其它易感基因的有害突变在3.7%的患者中检测,和大多数观察到的同源重组基因,包括PALB2(1.2%)和BARD1,RAD51D,RAD51C和BRIP1(0.3%至0.5%)。有基因突变的TNBC患者比那些没有突变的患者在较早的年龄被诊断(P <0.001),并且有较高级别的肿瘤(P= 0.01)。
结论:
在未选择癌症家族史的TNBC患者,易感基因的有害突变有较高的发生频率。突变发生率估计表明TNBC的患者,不管诊断的年龄或癌症的家族史,应考虑BRCA1和BRCA2生殖细胞基因检测。虽然其他的易感基因的突变也在TNBC患者中观察得到,但在这些突变用于真正的临床风险评估之前还需要更好的癌症风险估计。
北京桓兴肿瘤医院 桓兴医讯编译组 孙晓莹
2014年12月9日 星期二
Published online before print December 1, 2014, doi:10.1200/JCO.2014.57.1414JCO December 1, 2014JCO.2014.57.1414
Inherited Mutations in 17 Breast Cancer Susceptibility Genes Among a Large Triple-Negative Breast Cancer Cohort Unselected for Family History of Breast Cancer
Purpose Recent advances in DNA sequencing have led to the development of breast cancer susceptibility gene panels for germline genetic testing of patients. We assessed the frequency of mutations in 17 predisposition genes, including BRCA1and BRCA2, in a large cohort of patients with triple-negative breast cancer (TNBC) unselected for family history of breast or ovarian cancer to determine the utility of germline genetic testing for those with TNBC.
Patients and Methods Patients with TNBC (N = 1,824) unselected for family history of breast or ovarian cancer were recruited through 12 studies, and germline DNA was sequenced to identify mutations.
Results Deleterious mutations were identified in 14.6% of all patients. Of these, 11.2% had mutations in the BRCA1 (8.5%) and BRCA2 (2.7%) genes. Deleterious mutations in 15 other predisposition genes were detected in 3.7% of patients, with the majority observed in genes involved in homologous recombination, includingPALB2 (1.2%) and BARD1, RAD51D, RAD51C, and BRIP1 (0.3% to 0.5%). Patients with TNBC with mutations were diagnosed at an earlier age (P < .001) and had higher-grade tumors (P = .01) than those without mutations.
Conclusion Deleterious mutations in predisposition genes are present at high frequency in patients with TNBC unselected for family history of cancer. Mutation prevalence estimates suggest that patients with TNBC, regardless of age at diagnosis or family history of cancer, should be considered for germline genetic testing of BRCA1 and BRCA2. Although mutations in other predisposition genes are observed among patients with TNBC, better cancer risk estimates are needed before these mutations are used for clinical risk assessment in relatives.
http://jco.ascopubs.org/content/early/2014/12/01/JCO.2014.57.1414.abstract

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