TY - JOUR
T1 - The landscape of somatic mutations in Indonesian cervical cancer is predominated by the PI3K pathway
AU - Spaans, Vivian M.
AU - Nyoman Bayu Mahendra, I.
AU - Purwoto, Gatot
AU - Trietsch, Marjolijn D.
AU - Osse, Michelle
AU - ter Haar, Natalja
AU - Peters, Alexander A.W.
AU - Fleuren, Gert J.
AU - Jordanova, Ekaterina S.
N1 - Publisher Copyright:
© 2017
PY - 2018/1
Y1 - 2018/1
N2 - Objective To investigate the prevalence of somatic mutations in Indonesian cervical carcinoma patients in the context of histology and human papillomavirus (HPV) type. Methods In total 174 somatic hot-spot mutations in 13 genes were analyzed by mass spectrometry in 137 Indonesian cervical carcinomas. Results In 66/137 tumors (48%) 95 mutations were identified. PIK3CA was most frequently mutated (24%), followed by FBXW7 (7%), CTNNB1 (6%), and PTEN (6%). In squamous cell carcinomas more often multiple mutations per sample (p = 0.040), and more PIK3CA (p = 0.039) and CTNNB1 (p = 0.038) mutations were detected compared to adenocarcinomas. PIK3CA mutations were associated with HPV 16 positivity, CDKN2A mutations with HPV 52 positivity, and, interestingly, PTEN mutations with HPV negativity. Balinese tumor samples more often carried multiple mutations (p = 0.019), and more CTNNB1, CDKN2A, and NRAS mutations compared to Javanese tumor samples. Conclusions Potentially targetable somatic mutations occurred in 48% of Indonesian cervical carcinomas. The landscape of mutations is predominated by mutations concerning the PI3K pathway, and we prompt for more research on developing therapies targeting this pathway, explicitly for the more advanced stage cervical carcinoma patients.
AB - Objective To investigate the prevalence of somatic mutations in Indonesian cervical carcinoma patients in the context of histology and human papillomavirus (HPV) type. Methods In total 174 somatic hot-spot mutations in 13 genes were analyzed by mass spectrometry in 137 Indonesian cervical carcinomas. Results In 66/137 tumors (48%) 95 mutations were identified. PIK3CA was most frequently mutated (24%), followed by FBXW7 (7%), CTNNB1 (6%), and PTEN (6%). In squamous cell carcinomas more often multiple mutations per sample (p = 0.040), and more PIK3CA (p = 0.039) and CTNNB1 (p = 0.038) mutations were detected compared to adenocarcinomas. PIK3CA mutations were associated with HPV 16 positivity, CDKN2A mutations with HPV 52 positivity, and, interestingly, PTEN mutations with HPV negativity. Balinese tumor samples more often carried multiple mutations (p = 0.019), and more CTNNB1, CDKN2A, and NRAS mutations compared to Javanese tumor samples. Conclusions Potentially targetable somatic mutations occurred in 48% of Indonesian cervical carcinomas. The landscape of mutations is predominated by mutations concerning the PI3K pathway, and we prompt for more research on developing therapies targeting this pathway, explicitly for the more advanced stage cervical carcinoma patients.
KW - Cervical carcinoma
KW - Indonesia
KW - PIK3CA
KW - cancer genomics
KW - human papillomavirus
KW - somatic mutation
KW - targeting therapy
UR - http://www.scopus.com/inward/record.url?scp=85032811814&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2017.10.009
DO - 10.1016/j.ygyno.2017.10.009
M3 - Article
C2 - 29113722
AN - SCOPUS:85032811814
SN - 0090-8258
VL - 148
SP - 189
EP - 196
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 1
ER -
