Cell-Free Circulating Tumor Dna (Cftdna) - In Cervical Carcinoma- A Future Directives As Diagnostic Marker.

Back ground: 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 and at early recurrence of Cell-free circulating tumor DNA (CFTDNA). Also to know its utilization in prognostication and to guide for genomically matched therapy. Methods and Material: A total of 25 patients with locally advanced squamous cell carcinoma of cervical cancer (Stage IB-IIIB) were tested prospectively with 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. Results: Average patient age was 51.57yrs(range 30-83yrs) and all patients were squamous cell carcinoma. In 21/25(84%) patients, CFTDNA was detected and sufficient to carry under NGS. Out of 50 genes, around 32 genetic alteration were detected. Mean genetic alteration was 4.08(2-14). In 3/25 (12%) patients are more than 8 genomic alteration detected, 5/25(20%) patients had 5-8 genetic alteration, remaining 13/25(52%) patients had less than 4 genetic alteration. Most common SNVs detected included were, TP53 -11/21 (52.3%) patients, CDKN2A- 10/21(47.6%)patients, PTEN and STK11 -7/21 (33.3%)patients, BRAF and VHL -6/21 (28.5%)patients, EGFR and SMAD4 -4/21(19%), CTNNB1, GNAS, KIT, APC, PIK3CA- 3/21 (14.28%)patients, SMARCB1, SMO, RET, FBXW7, ERBB2, CSF1R, CDH1, AKT1, ATM, EBB4, FGFR3, FLT3, HRAS, JAK3, MET, NOTCH1, NPM1, KRAS, PTPN11- 1 or 2/21(4.7 to 9.5%) patients. On combination of these genetic alterations - EGFR, KIT, PTEN, PIK3CA, TP 53, VHL are the main alterations and combination of these gene (Diagnostic GENETIC MODULE), at least one genetic alteration among combination was found in 100% patients at any point of time. Further follow up data regarding correlation of these genetic alteration with prognosis will follows. Conclusions: CfTDNA can be easily demonstrable and can be used as non- invasive diagnostic tool in cervical carcinoma. Further, to create proper genetic module as diagnostic and prognostic marker- continuation of the study in large scale with different race, ethnicity and country required. [ABSTRACT FROM AUTHOR]