Prevalence and spectrum of AKT1, PIK3CA, PTEN and TP53 somatic mutations in Chinese breast cancer patients

PLoS One. 2018 Sep 13;13(9):e0203495. doi: 10.1371/journal.pone.0203495. eCollection 2018.


Breast cancer, one of the most frequently occurring cancers worldwide, is the leading cause of cancer-related death among women. AKT1, PIK3CA, PTEN and TP53 mutations were common observed in breast cancer representing potential clinical biomarkers for cancer classification and treatment. A comprehensive knowledge of AKT1, PIK3CA, PTEN and TP53 mutations in breast cancer was still insufficient in Chinese population. In this study, the complete coding regions and exon-intron boundaries of AKT1, PIK3CA, PTEN and TP53 genes were sequenced in paired breast tumor and normal tissues from 313 Chinese breast cancer patients using microfluidic PCR-based target enrichment and next-generation sequencing technology. Total 120 somatic mutations were identified in 190 of the 313 patients (60.7%), with the mutation frequency of AKT1 as 3.2%, PIK3CA as 36.4%, PTEN as 4.8%, and TP53 as 33.9%. Among these mutations, 1 in PIK3CA (p.I69N), 3 in PTEN (p.K62X, c.635-12_636delTTAACCATGCAGAT and p.N340IfsTer4) and 5 in TP53 (p.Q136AfsTer5, p.K139_P142del, p.Y234dup, p.V274LfsTer31 and p.N310TfsTer35) were novel. Notably, PIK3CA somatic mutations were significantly associated with ER-positive or PR-positive tumors. TP53 somatic mutations were significantly associated with ER-negative, PR-negative, HER2-positive, BRCA1 mutation, Ki67 high expression and basal-like tumors. Our findings provided a comprehensive mutation profiling of AKT1, PIK3CA, PTEN and TP53 genes in Chinese breast cancer patients, which have potential implications in clinical management.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Asian People
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • China / epidemiology
  • Class I Phosphatidylinositol 3-Kinases / genetics*
  • Female
  • Humans
  • Middle Aged
  • PTEN Phosphohydrolase / genetics*
  • Proto-Oncogene Proteins c-akt / genetics*
  • Tumor Suppressor Protein p53 / genetics*


  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human

Grant support

This work was supported in part by grant from the Natural Science Foundation of China (No. 81372228), and grants from China Hunan Provincial Science and Technology Department (No. 2016GK3022, 2016XK2033 and 2016JC2068). Sanway Gene Technology Inc. provided support in the form of salaries for the specified authors (XWG, MC, LMP, XXX, JLL, LZD and JW), but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the “Author Contributions” section.