Multigene clinical mutational profiling of breast carcinoma using next-generation sequencing

Sinchita Roy-Chowdhuri, Debora De Melo Gagliato, Mark J. Routbort, Keyur P. Patel, Rajesh R. Singh, Russell Broaddus, Alexander J. Lazar, Aysegul Sahin, Ricardo H. Alvarez, Stacy Moulder, Jennifer J. Wheler, Filip Janku, Ana M. Gonzalez-Angulo, Mariana Chavez-MacGregor, Vicente Valero, Naoto T. Ueno, Gordon Mills, John Mendelsohn, Hui Yao, Kenneth AldapeRajyalakshmi Luthra, Funda Meric-Bernstam

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Objectives: The advent of next-generation sequencing (NGS) platforms in the realm of clinical molecular diagnostics provides multigene mutational profiling through massively parallel sequencing. Methods: We analyzed 415 breast carcinoma samples from 354 patients using NGS in known hotspots of 46 commonly known cancer-causing genes. Results: A total of 281 somatic nonsynonymous mutations were detected in 62.1% of patients. TP53 was most frequently mutated (38.8%), followed by PIK3CA (31.7%), AKT1 (6%), and ATM (3.9%), with other mutations detected at a lower frequency. When stratified into clinically relevant therapeutic groups (estrogen receptor [ER]/progesterone receptor [PR]+ human epidermal growth factor receptor 2 [HER2]-, ER/PR+HER2+, ER/PR-HER2+, ER/PR/HER2-), each group showed distinct mutational profiles. The ER/PR+HER2- tumors (n = 132) showed the highest frequency of PIK3CA mutations (38%), while the triple-negative tumors (n = 64) had a significantly higher number of TP53 mutations (62%). Of the 61 patients tested for both primary and metastatic tumors, concordant results were seen in 47 (77%) patients, while 13 patients showed additional mutations in the metastasis. Conclusions: Our results indicate that breast cancers may harbor potentially actionable mutations for targeted therapeutics. Therefore, NGS-based mutational profiling can provide useful information that can guide targeted cancer therapy.

Original languageEnglish (US)
Pages (from-to)713-721
Number of pages9
JournalAmerican journal of clinical pathology
Issue number5
StatePublished - Nov 2015
Externally publishedYes


  • Breast carcinoma
  • ER positive
  • Mutational profiling
  • Next-generation sequencing
  • Triple negative

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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