TY - EJOU
AU - Chang, Ya-Sian
AU - Chang, Chieh-Min
AU - Lin, Chien-Yu
AU - Chao, Dy-San
AU - Huang, Hsi-Yuan
AU - Chang, Jan-Gowth
TI - Pathway Mutations in Breast Cancer Using Whole-Exome Sequencing
T2 - Oncology Research
PY - 2020
VL - 28
IS - 2
SN - 1555-3906
AB - The genomic landscape of breast cancer (BC) is complex. The purpose of this study was to decipher the mutational profiles of Taiwanese patients with BC using next-generation sequencing. We performed whole-exome
sequencing on DNA from 24 tumor tissue specimens from BC patients. Sanger sequencing was used to validate the identified variants. Sanger sequencing was also performed on paired adjacent nontumor tissues. After
genotype calling and algorithmic annotations, we identified 49 deleterious variants in canonical cancer-related
genes in our BC cohort. The most frequently mutated genes were PIK3CA (16.67%), FKBP9 (12.5%), TP53
(12.5%), ATM (8.33%), CHEK2 (8.33%), FOXO3 (8.33%), NTRK1 (8.33%), and NUTM2B (8.33%). Seven
mutated variants (ATR p.V1581fs, CSF1R p.R579Q, GATA3 p.T356delinsTMKS, LRP5 p.W389*, MAP3K1
p.T918fs, MET p.K1161fs, and MTR p.P1178S) were novel variants that are not present in any gene mutation
database. After grouping the samples according to molecular subtype, we found that the cell cycle, MAPK,
and chemokine signaling pathways in the luminal A subtype of BC; the focal adhesion, axon guidance, and
endocytosis pathways in the luminal B subtype; and amyotrophic lateral sclerosis in the basal-like subtype
were exclusively altered. Survival curve analysis showed that the presence of the MAPK signaling pathway
and endocytosis mutations were correlated with a poor prognosis. These survival data were consistent with
cBioPortal analyses of 2,051 BC cases. We discovered novel mutations in patients with BC. These results have
implications for developing strategic, adjuvant, and gene-targeted therapies.
KW - Breast cancer (BC); Whole-exome sequencing; Gene mutation; Pathway mutation
DO - 10.3727/096504019X15698362825407