@Article{096504019X15698362825407,
AUTHOR = {Ya-Sian Chang, Chieh-Min Chang, Chien-Yu Lin, Dy-San Chao, Hsi-Yuan Huang, Jan-Gowth Chang},
TITLE = {Pathway Mutations in Breast Cancer Using Whole-Exome Sequencing},
JOURNAL = {Oncology Research},
VOLUME = {28},
YEAR = {2020},
NUMBER = {2},
PAGES = {107--116},
URL = {http://www.techscience.com/or/v28n2/48536},
ISSN = {1555-3906},
ABSTRACT = {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 <i>PIK3CA</i> (16.67%), <i>FKBP9</i> (12.5%), <i>TP53 </i>
(12.5%), <i>ATM</i> (8.33%), <i>CHEK2</i> (8.33%), <i>FOXO3 </i>(8.33%), <i>NTRK1</i> (8.33%), and <i>NUTM2B</i> (8.33%). Seven 
mutated variants (<i>ATR</i> p.V1581fs, <i>CSF1R</i> p.R579Q, <i>GATA3</i> p.T356delinsTMKS, LRP5 p.W389*, <i>MAP3K1</i>
p.T918fs, <i>MET</i> p.K1161fs, and <i>MTR</i> 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.},
DOI = {10.3727/096504019X15698362825407}
}