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A Pilot Study Based on the Correlation Between Whole Exome and Transcriptome Reveals Potent Variants in the Indian Population of Cervical Cancer

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Abstract

Cervical malignancy (CC) is the 2nd most prevalent malignancy among females, leading to cancer mortality. Primary detection of CC tumors results in an improved prognosis. CC is a malignant gynecological tumor, with few treatment options. New diagnostic and therapeutic agents are required to expand patient survival and quality of life. If CC tumors can be found at an early stage, the prognosis is much brighter. New diagnostic and therapeutic agents are needed to increase patient survival and quality of life. In this work, we performed whole-exome sequencing utilizing V5 (Illumina platform) 10 samples, 5 control and 5 CC tumour tissue, and we compared the results with transcriptome studies. KMT2C variations were shown to be among the most vicious in this analysis. From an Indian viewpoint, we found a plethora of SNVs and mutations, including those with known, unknown, and possible effects on health. Based on our findings, we know that the KMT2C gene is on chr. Seven and in exon 8, all three recognized variants are missense, synonymous, coding synonymous, non-coding variants, and GnomAD MAF (− 0.05). The variation at position (7:152265091, T > A, SNV 62478356) in KMT2C is unique, potent, and pathogenic. The missense coding transcript CIQTNF maps to chromosome 7 and displays T > C SNV. In addition, we performed single strand conformational polymorphism analysis on 64 samples and further confirmed them using Sanger sequencing to understand and verify the mutations. KMT2C shows a log FC value of − 1.16. Understanding emerging harmful mutations from an Indian viewpoint is facilitated by our bioinformatics-based, extensive correlation studies of WES analysis. Potentially harmful and new mutations were found in our preliminary analysis; among these ten top mutated genes, KMT2C and CIQTNF were altered in ten cases of CC with an Indian phenotype.

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Data Availability

All raw reads are available through NCBI-SRA PRJNA Bio project submission: SUB10812780. The microarray data has been deposited in the GEO database under accession number GSE127265 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE127265). If you have any inquiries, please contact the respective author.

Abbreviations

CC:

Cervical Cancer

AHG:

Affymetrix human genome

CSCC:

Cervical squamous cell carcinoma

GEO:

Gene expression Omnibus

TCGA:

Cancer Genome Atlas

WES:

Whole exome sequencing

FDR:

False discovery rate

NGS:

Next generation sequencing

AGCC:

Affymetrix GeneChip® Command Console

KM:

Kaplan–Mayer

AEC:

Affymetrix expression console

FFPE:

Formalin-fixed paraffin-embedded

TAC:

Transcriptome analysis console

HCD:

Human Clariom D

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Acknowledgements

We gratefully acknowledge the support from MNJ Hospital, Hyderabad, for the ethical committee towards kind assistance of tissue sampling. We sincerely acknowledge SCP for her support. We are greatly indebted to Bioclues.org and its founder, PS, for his valuable time and energy in helping with data analysis and editing the complete manuscript preparations. We gratefully acknowledge the resources provided by BISR, Jaipur, Rajasthan. We specially acknowledge  Dr. Ashwani Kumari, DNA Xperts Ashwani for performing Whole Exome Sequencing and clearing all our queries. We thank the Department of Genetics and Biotechnology, Osmania University, Hyderabad, School of Bioengineering and Biosciences, Lovely Professional University, Jalandhar, Punjab, and GenepoweRx (K&H Personalized Medicine Clinic), Hyderabad, Telangana, India for their support and encouragement.

Funding

Prof. Smita C. Pawar received funds supporting this project from the Science and Engineering Research Board (SERB), India (EEQ/ 2019/000569), on January 6, 2020.

Author information

Authors and Affiliations

  1. School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Jalandhar, India

    Santosh Kumari Duppala, Bhumandeep Kour & Ashish Vyas

  2. Department of Genetics and Biotechnology, University College of Science, Osmania University, Hyderabad, Telangana, 500007, India

    Pavan Kumar Poleboyina, Govardhan Bale & Smita C. Pawar

  3. Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri, Clappana, Kerala, 690525, India

    Prashanth N. Suravajhala

  4. GenepoweRx, K&H Personalized Medicine Clinic, Jubilee Hills, Hyderabad, Telangana, 500033, India

    Sugunakar Vuree

  5. Bioclues.org, Hyderabad, Telangana, India

    Prashanth N. Suravajhala & Sugunakar Vuree

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  1. Santosh Kumari Duppala
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Contributions

Sugunakar Vuree (SGV), Smita C. Pawar (SCP) and Prashanth Suravajhala (PS) conceived the idea. Santosh Kumari Duppala (SKD)is the first author who wrote the manuscript and performed analysis. SKD, SGV and PS analysed the data and interpreted the whole manuscript. Pavan Kumar Poleboyina (PKB), Bhumandeep Kour (BK), Ashish Vyas (AV), and Govardhan Bale (GB) performed lateral analyses. PS and SGV critically reviewed and proofread the manuscript. All the authors have read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Smita C. Pawar, Prashanth N. Suravajhala or Sugunakar Vuree.

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Conflict of interest

The authors didn’t have any competing interests.

Ethical Approval

All the institutional guidelines and ethical clearance are carried out from MNJ Hospital Hyderabad Telangana (Regd No: ECR/227/Inst/AP/2013/RR-19) with an approval date of 20 Jan 2020.

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Duppala, S.K., Poleboyina, P.K., Kour, B. et al. A Pilot Study Based on the Correlation Between Whole Exome and Transcriptome Reveals Potent Variants in the Indian Population of Cervical Cancer. Indian J Microbiol (2024). https://doi.org/10.1007/s12088-024-01295-6

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