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Mutational Aberrations Detected in Mucinous Epithelial Ovarian Cancer of Asian Women
  1. Wen Yee Chay, MBBS, MRCP*,
  2. Li Lian Kwok, Msc,
  3. Wen Ning Tiong,
  4. Sai Sakktee Krisna, BSc (Hons)§,
  5. Kiat Hon Lim, MBBS, FRCPath, FRCPA,
  6. N. Gopalkrishna Iyer, MBBS (Hons), PhD, FRCSEd, FAMS§,,
  7. Liang Kee Goh, MTech, PhD# and
  8. Daniel Shao-Weng Tan, BSc (Hons), MBBS, MRCP, FAMS*,§
  1. * Departments of Medical Oncology and
  2. Clinical Trials and Epidemiology, National Cancer Centre Singapore;
  3. School of Biological Sciences, Nanyang Technological University, Singapore;
  4. § Cancer Therapeutics Research Laboratory, National Cancer Centre Singapore;
  5. Department of Anatomical Pathology, Singapore General Hospital; and
  6. Division of Surgical Oncology, National Cancer Centre Singapore; and
  7. # Cancer and Stem Cell Biology, Duke-National University of Singapore, Singapore.
  1. Address correspondence and reprint requests to Wen Yee Chay, MBBS, MRCP, Department of Medical Oncology, National Cancer Centre Singapore, 11 Hospital Drive, Singapore 169610. E-mail: chay.wen.yee{at}


Background Mucinous epithelial ovarian cancers (mEOCs) respond poorly to conventional chemotherapy and have a poor prognosis in advanced stages. The genomic landscape for mEOC in the Asian settings is ill defined. We seek to identify various mutational aberrations present in mEOC and correlate them with clinical outcomes.

Methods A total of 199 cases of mEOC were identified from a prospectively maintained gynecologic oncology tumor database. DNA was extracted and analyzed for KRAS mutations by using Sanger sequencing. Further MassArray sequencing was performed on 45 samples. Clinicopathologic correlation was performed with the results obtained.

Findings KRAS mutation status was evaluable in 124 cases. Fifty-five percent (68/124) were KRAS negative, whereas 45% (56/124) harbored a KRAS mutation, lower than that in Western populations. Successful ascertainment of both KRAS and HER2 statuses by Sanger sequencing occurred for 105 cases. The proportion of the double-positive subtype (HER2+ and KRAS positive) was 8% (8/105); double-negative subtype (HER2− and KRAS negative), 34% (36/105); and cases with mutation in either KRAS or HER2, 58% (61/105). The KRAS mutation rate was 44%, 50%, and 29% among Chinese, Indians, and Malays, respectively. There was no significant difference in overall survival (P = 0.952) or progression-free survival (P = 0.635) between KRAS-positive and KRAS-negative patients. Similar results were observed for progression-free survival (P = 0.206) and overall survival (P = 0.440) when outcomes were examined between the 4 groups based on KRAS and HER2 mutation. Patients in the double-negative mutation subgroup had higher risk for death/progression compared with patients in the other 3 mutation subgroups. Further MassARRAY multiplexed profiling was performed in patients with sufficient DNA material (n = 45) and yielded KRAS mutations (n = 16), PDGFRA mutations (n = 3), PIK3CA (n = 1) and KIT (n = 1), and HRAS, FGFR, MET, and NRAS (n = 1 each).

Conclusions Our study provides further knowledge about the mutational aberrations in mEOC in Asian populations. Neither the presence of KRAS mutation nor their correlation with HER2 mutations influenced outcomes.

  • Mucinous epithelial ovarian cancers
  • KRAS
  • HER2
  • MassArray sequencing
  • Sanger sequencing

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  • The authors declare no conflicts of interest.