Abstract P3-04-09: Integrated analysis of genetic variations in Chinese breast cancer from a single institution
Authors: Liao N , Zhang G-C , Wang Y , Cao L , Li K , Ren C-Y , Wen L-Z , Shi Y , Zhu W , Chen X 
Published: February 2018

Abstract
To investigate the characteristics of somatic mutation or copy number variations in Chinese breast cancer, tumor tissues from 105 patients diagnosed at age from 26 to 81 (median age 48) were assessed by next-generation sequencing technology using a customized panel, including 33 genes of putative tumor suppressors or oncogenes. At least one genetic alteration (including mutations, copy number variations and fusion genes) was observed in 99/105 (94%) samples. Similar to the previous report in TCGA dataset, TP53 (49%) and PIK3CA (43%) were the most frequently mutated genes, which occurred in a significant mutual exclusive manner (p&lt;0.05). Three genes including MYC copy number amplification (35%), FGFR1 (19%) and GATA3 mutation (16%) were altered at the frequency of &gt;10% in our dataset, in which the occurrence of MYC amplification was higher than the TCGA cohort (22%, p&lt;0.05). Importantly, we identified four fusion genes of FGFR1 including one previously reported (TACC1-FGFR1) and three novel fusion ones (MIR1268A-FGFR1, LZTS1-AS1-FGFR1, and LINC01605-FGFR1). Unlike the high prevalence of CCND1 amplification (17%) and CDH1 mutations (13%) in TCGA dataset, genetic variations of CCND1 and CDH1 in our study occurred at a low frequency with 2% and 4%, respectively (p&lt;0.05). In addition, we also identified three novel ESR1 mutations (ESR1 G74R, D230H and M250T) in the untreated patients with early breast cancer. Furthermore, nonnegative matrix factorization (NMF) clustering of genetic variations revealed five distinct molecular classes in our dataset. NMF class I was characterized by a high rate of HR+/ERBB2- tumors (80%) and genetic alterations of FGFR1 (100%). A gain of ERBB2 gene was observed in 93% of NMF class II along with TOP2A amplification in 57% of HR+/ERBB2+ tumors. NMF class III was characterized by a high rate of HR+/ERBB2- (95%) and GATA3 mutations (75%) without TP53 mutation. The characteristics of NMF class IV were the high rate of PIK3CA mutations (95%) and HR+/ERBB2- tumors (75%) along with low rate of TP53 mutations. More HR-/ERBB2- tumors (39%) were observed in NMF class V with a high rate of MYC amplification (82%) and TP53 mutation (89%). Further analysis in the TCGA cohort revealed the patients in NMF class V had the shorter survival time than other clusters. Collectively, we identified several novel genetic variations and generated a preliminary profile of somatic genetic aberrations that could classify Chinese breast cancer in this study, and may represent novel therapeutic targets for molecular subsets of breast cancer.
This study was supported in part by National Natural Science Foundation of China (8160111571) and Guangdong Natural Science Foundation (2016A030313768).
Citation Format: Liao N, Zhang G-C, Wang Y, Cao L, Li K, Ren C-Y, Wen L-Z, Shi Y, Zhu W, Chen X. Integrated analysis of genetic variations in Chinese breast cancer from a single institution [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-04-09.