Cell-free circulating tumor DNA mutation profiling for cervical carcinoma as diagnostic biomarker: A 50-genes module to future directive
Govardhan HB1, Khaleel IA1, Shubha SA1, Manisha R1, Nivedita S1, Noopur N1, Jayashree NP1, Fareena T1 and Sweta K1
1 Department of Radiation Oncology, Kidwai Cancer Institute, Bangalore, Karnataka, India
Correspondence:
Govardhan HB, email:
Keywords: cervical carcinoma; cfTDNA; next generation sequencing; minimally-invasive; biomarker
Received: November 08, 2018 Accepted: January 04, 2019 Published: January 13, 2019
Abstract
Introduction: Currently, tissue biopsy is the gold-standard to verify carcinoma of uterine cervix initial diagnosis and can be challenging due to its invasive nature. In this study, our objective was a non-invasive genetic panel for timely detection of cervical carcinoma and its progression using cell-free tumour DNA (cfTDNA).
Materials and Methods: 25 cervical carcinoma patients were tested with a 50-gene tumour panel. cfTDNA isolated from serum was checked for single nucleotide variations (SNVs) or copy number alterations (CNAs) using targeted Next Generation Sequencing (NGS), with further validation of results by checking respective formalin-fixed paraffin-embedded (FFPE) tumor tissues for the same genetic alterations.
Results: 32/50 genes were detected in the serum samples. The SNVs detected included TP53 in 52.3% patients, CDKN2A in 47.6%, PTEN and STK11 in 33.3% patients, BRAF and VHL in 28.5% patients, EGFR and SMAD4 in 19% patients; CTNNB1, GNAS, KIT, APC, PIK3CA in 14.28% patients; SMARCB1, SMO, RET, FBXW7, ERBB2, CSF1R, CDH1, AKT1, ATM, EBB4, FGFR3, FLT3, HRAS, JAK3, MET, NOTCH1, NPM1, KRAS, PTPN11 in 4.7 to 9.5% patients.
Conclusions: These findings illustrate that cfTDNA is easily demonstrable and can be used as a surrogate for tissue biopsy in uterine cervix carcinoma.
