Cell-Free Circulating Tumor DNA Mutation Profiling for Cervical Carcinoma as Diagnostic Biomarker: A 50-Gene Module to Future Directive
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Across the globe, cervical cancer is the most common female malignancy, second only to breast cancer, as in both incidence and mortality. 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 noninvasive genetic panel for timely detection of cervical carcinoma and its progression using cell-free tumor DNA (ctDNA).
Twenty-five cervical carcinoma patients were tested with a 50-gene tumor panel. ctDNA isolated from serum was checked for single-nucleotide variations (SNVs) or copy number alterations using targeted next-generation sequencing, with further validation of results by checking respective formalin-fixed paraffin-embedded tumor tissues for the same genetic alterations.
Out of 50 genes, 32 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. On combining alterations in BRAF, CDKN2A, EGFR, PIK3CA, PTEN, STK11, TP53 and VHL genes, at least one of the genetic alterations was found in 100% patients.
These findings illustrate that ctDNA is easily demonstrable and can be used as a surrogate for tissue biopsy in uterine cervix carcinoma.
KeywordsCervical carcinoma ctDNA Next-generation sequencing Minimally invasive Biomarker
We acknowledge the contributions by Govardhan HB and Khaleel IA who conceived and designed the study protocol; Shubha S A who was responsible for acquisition of data; Manisha R for autonomously writing, reviewing and/or revising the manuscript; Nivedita S and Noopur N who provided technical support and study supervision; and Jayashree NP, Fareena T and Sweta K who gave help during the course of the study.
Compliance with Ethical Standards
Conflict of interest
The authors declare no conflicts of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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