Vivian M Spaans1, I Nyoman Bayu Mahendra2, Gatot Purwoto3, Marjolijn D Trietsch4, Michelle Osse5, Natalja Ter Haar6, Alexander A W Peters7, Gert J Fleuren8, Ekaterina S Jordanova9. 1. Department of Obstetrics and Gynecology, Leiden University Medical Center, Leiden, The Netherlands; Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: V.M.Spaans@lumc.nl. 2. Department of Obstetrics and Gynecology, Faculty of Medicine, Udayana University, Denpasar, Bali, Indonesia. 3. Department of Gynecology and Obstetrics, Faculty of Medicine, University of Indonesia, Rumah Sakit Dr. Cipto Mangunkusumo, Jakarta, Java, Indonesia. 4. Department of Obstetrics and Gynecology, Leiden University Medical Center, Leiden, The Netherlands; Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: M.D.Trietsch@lumc.nl. 5. Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: E.M.Osse@lumc.nl. 6. Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: N.T.ter_Haar@lumc.nl. 7. Department of Obstetrics and Gynecology, Leiden University Medical Center, Leiden, The Netherlands. 8. Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: G.J.Fleuren@lumc.nl. 9. Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands; Center for Gynecologic Oncology, Amsterdam, The Netherlands. Electronic address: E.S.Jordanova@lumc.nl.
Abstract
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.
OBJECTIVE: To investigate the prevalence of somatic mutations in Indonesian cervical carcinomapatients 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 carcinomapatients.
Authors: I Putu Yuda Prabawa; Agha Bhargah; Firdy Liwang; Deasy Ayuningtyas Tandio; Aditya Leonard Tandio; Anak Agung Wiradewi Lestari; I Nyoman Gede Budiana; Ida Bagus Amertha Putra Manuaba Journal: Asian Pac J Cancer Prev Date: 2019-03-26