Concordance of genomic alterations between primary and recurrent breast cancer.
Concordance of genomic alterations between primary and recurrent breast cancer.
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DOI：
10.1158/1535-7163.mct-13-0482
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发表时间：
2014-05
影响因子：
5.7
通讯作者：
Gonzalez-Angulo AM
中科院分区：
文献类型：
--
作者：
Meric-Bernstam F;Frampton GM;Ferrer-Lozano J;Yelensky R;Pérez-Fidalgo JA;Wang Y;Palmer GA;Ross JS;Miller VA;Su X;Eroles P;Barrera JA;Burgues O;Lluch AM;Zheng X;Sahin A;Stephens PJ;Mills GB;Cronin MT;Gonzalez-Angulo AM
There is growing interest in delivering genomically-informed cancer therapy. Our aim was to determine the concordance of genomic alterations between primary and recurrent breast cancer. Targeted next generation sequencing was performed on formalin-fixed paraffin embedded (FFPE) samples, profiling 3320 exons of 182 cancer-related genes plus 37 introns from 14 genes often rearranged in cancer. Point mutations, indels, copy number alterations and select rearrangements were assessed in 74 tumors from 43 patients (36 primary, 38 recurrence/metastases). Alterations potentially targetable with established or investigational therapeutics were considered “actionable”. Alterations were detected in 55 genes (mean 3.95 alterations/sample, range 1-12), including mutations in PIK3CA, TP53, ARID1A, PTEN, AKT1, NF1, FBXW7 and FGFR3 and amplifications in MCL1, CCND1, FGFR1, MYC, IGF1R, MDM2, MDM4, AKT3, CDK4, AKT2. In 33 matched primary and recurrent tumors, 97 of 112 (86.6%) somatic mutations were concordant. Of identified copy number alterations, 136 of 159 (85.5%) were concordant: 37 (23.3%) were concordant, but below the reporting threshold in one of the matched samples, and 23 (14.5%) discordant. There was an increased frequency of CDK4/MDM2 amplifications in recurrences, as well as gains and losses of other actionable alterations. 40 of 43 (93%) patients had actionable alterations that could inform targeted treatment options. In conclusion, deep genomic profiling of cancer-related genes reveals potentially actionable alterations in most breast cancer patients. Overall there was high concordance between primary and recurrent tumors. Analysis of recurrent tumors prior to treatment may provide additional insights, as both gains and losses of targets are observed.
