Cancer Genetics Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4029, Australia,
Breast Cancer Res Treat. 2014 Jan;143(2):385-92. doi: 10.1007/s10549-013-2798-1. Epub 2013 Dec 7.
Basal-like and triple-negative breast cancers usually display a high level of genomic instability and often carry TP53 mutations. Mutations in EGFR have been reported in about 10 % triple-negative tumours from Chinese women, and there is some evidence that triple-negative and basal-like tumours might carry additional mutations against which targeted therapies are available. We, therefore, sought to determine the frequency of 238 targetable mutations in 19 oncogenes (including EGFR) in a panel of basal-like and triple-negative breast cancers from Caucasian women. We used the OncoCarta panel to screen for 238 mutations across 19 common oncogenes in 107 basal-like and triple-negative breast cancers from Caucasian women. Mutations were then verified using Sanger sequencing or primer extension by iPLEX. We identified and validated 10 mutations across five genes. Most of the mutations were observed in the PIK3CA gene (18/107, 16.8 %), while mutations in KRAS, NRAS, MET and AKT1 were present in only one tumour each (1/107, 0.9 %). Among the missense substitutions in PIK3CA the point mutation resulting in the amino acid change H1047R was the most frequent (8/18, 44 %). All mutations were mutually exclusive, apart from one basal-like breast tumour which harboured mutations in both MET (p.T992I) and PIK3CA (p.H1047R). We did not identify any mutations in the EGFR gene. In conclusion, we found that with the exception of mutations in PIK3CA, these actionable oncogenic mutations on the Oncocarta panel are rare in basal-like and triple-negative breast cancers from Caucasian women. Custom panels, designed to detect mutations identified by exome sequencing of basal-like and triple-negative breast cancers, are, therefore, needed to identify women who might be eligible for targeted treatment.
基底样和三阴性乳腺癌通常表现出高水平的基因组不稳定性，并且经常携带 TP53 突变。据报道，在中国女性的大约 10%三阴性肿瘤中存在 EGFR 突变，并且有一些证据表明三阴性和基底样肿瘤可能携带其他针对靶向治疗有效的突变。因此，我们试图确定在一组来自白人女性的基底样和三阴性乳腺癌中，19 个致癌基因（包括 EGFR）中的 238 个可靶向突变的频率。我们使用 OncoCarta 面板在 107 例来自白人女性的基底样和三阴性乳腺癌中筛查 19 个常见致癌基因中的 238 个突变。然后使用 Sanger 测序或 iPLEX 引物延伸验证突变。我们在五个基因中鉴定并验证了 10 个突变。大多数突变发生在 PIK3CA 基因中（18/107，16.8%），而 KRAS、NRAS、MET 和 AKT1 中的突变在每个肿瘤中仅存在一个（1/107，0.9%）。在 PIK3CA 的错义取代中，导致氨基酸变化 H1047R 的点突变最为频繁（18/18，44%）。除了一个基底样乳腺癌肿瘤同时携带 MET（p.T992I）和 PIK3CA（p.H1047R）突变外，所有突变都是相互排斥的。我们在 EGFR 基因中未发现任何突变。总之，我们发现除了 PIK3CA 突变外，这些 Oncocarta 面板上可靶向的致癌突变在白人女性的基底样和三阴性乳腺癌中很少见。因此，需要设计专门用于检测基底样和三阴性乳腺癌外显子组测序中鉴定的突变的定制面板，以确定可能有资格接受靶向治疗的女性。
