There are many diagnostic modalities are developed or under development to improve the diagnostic ability and to prognosticate in patients with cervical carcinoma. Cell-free circulating tumor DNA (CFTDNA) is one among them. In this study we are aiming to know the diagnostic ability at diagnosis of CFTDNA and to create genetic screening tool to detect cervical carcioma.
A total of 25 patients with locally advanced squamous cell carcinoma of cervical cancer (stage IIA-IIIB) were tested prospectively with a 50-gene tumor panel in a NABL accredited laboratory. 4 ml serum was collected, CfTDNA was isolated and they were checked for single nucleotide variants (SNVs) genes/copy number variants (CNVs) by using NGS and tumor FFPE blocks were again rechecked by NGS or PCR for the same genetic alterations.
Average patient age was 50.5 (range 35-83). In 23/25 (88.8%) patients, CfTDNA was detected and sufficient to carry under NGS. Out of 50 genes, around 31 genetic alterations were detected. Mean genetic alteration was 4.7 (2-15). In 4/23 (17%) patients are more than 8 genomic alteration detected, 4/23 (17%) patients had 5-8 genetic alteration, remaining 15/23 (67%) patients had less than 4 genetic alteration. Most common SNVs detected included were, CDKN2A- 12/23 patients, PIK3CA-11/23 patients, TP53 -11/23 (87.5%) patients, PTEN -7/23 patients, BRAF-7/23 patients, STK11- 7/23 patients, VHL- 6/23 patients, EGFR, CTNNB1, GNAS, KIT, SMAD3 were 5/23 patients, SMARCB1, SMO, RET, FBXW7, ERBB2, CSF1R, CDH1, APC- 3/23 each, AKT1, EBB4, FGFR3, FGFR3. FLT3, HRAS, JAK3, MET, NOTCH1, NPM1, KRAS, PTPN11- 1 or 2/23 patients. On combination of these genetic alterations - EGFR, KIT, PTEN, PIK3CA, TP 53, VHL are the main alterations and combination of these gene (Govardhan Diagnostic and Screening Genetic Module for Cervix Cancer), at least one genetic alteration among combination was found in 100% patients at any point of time.
CfTDNA can be easily demonstrable and can be used as a noninvasive diagnostic tool in cervical carcinoma. The proposed genetic screening module needs to be further investigated at large scale with different races, ethnicities and countries.
Clinical trial identification
Legal entity responsible for the study
All authors have declared no conflicts of interest.