Multigene Clinical Mutational Profiling of Breast Carcinoma Using Next-Generation Sequencing. Issue 5 (1st November 2015)

• Record Type: Journal Article
• Authors: Roy-Chowdhuri, Sinchita; de Melo Gagliato, Debora; Routbort, Mark J.; Patel, Keyur P.; Singh, Rajesh R.; Broaddus, Russell; Lazar, Alexander J.; Sahin, Aysegul; Alvarez, Ricardo H.; Moulder, Stacy; Wheler, Jennifer J.; Janku, Filip; Gonzalez-Angulo, Ana M.; Chavez-MacGregor, Mariana; Valero, Vicente; Ueno, Naoto T.; Mills, Gordon; Mendelsohn, John; Yao, Hui; Aldape, Kenneth; Luthra, Rajyalakshmi; Meric-Bernstam, Funda
• Is Part Of: American journal of clinical pathology. Volume 144:Issue 5(2015)
• Page Start: 713
• Page End: 721
• Publication Date: 2015-11-01
• Subjects: Next-generation sequencing -- Breast carcinoma -- Mutational profiling -- ER positive -- Triple negative; Diagnosis, Laboratory -- Periodicals; Pathology -- Periodicals; 616.07
• DOI: 10.1309/AJCPWDEQYCYC92JQ
• Languages: English
• ISSNs: 0002-9173

Abstract

Abstract: 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.