KRAS Mutation Subtypes and Their Association with Other Driver Mutations in Oncogenic Pathways

Author:

Mondal Koushik12ORCID,Posa Mahesh Kumar3,Shenoy Revathi P.4ORCID,Roychoudhury Susanta15ORCID

Affiliation:

1. Division of Basic & Translational Research, Saroj Gupta Cancer Centre & Research Institute, MG Road, Kolkata 700063, West Bengal, India

2. Department of Cancer Immunology, SwasthyaNiketan Integrated Healthcare & Research Foundation, Koramangala, Bengaluru 560034, Karnataka, India

3. School of Pharmaceutical Sciences, Jaipur National University, Jagatpura, Jaipur 302017, Rajasthan, India

4. Department of Biochemistry, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India

5. CSIR-Indian Institute of Chemical Biology, 4 Raja S.C.Mullick Road, Jadavpur, Kolkata 700032, West Bengal, India

Abstract

The KRAS mutation stands out as one of the most influential oncogenic mutations, which directly regulates the hallmark features of cancer and interacts with other cancer-causing driver mutations. However, there remains a lack of precise information on their cooccurrence with mutated variants of KRAS and any correlations between KRAS and other driver mutations. To enquire about this issue, we delved into cBioPortal, TCGA, UALCAN, and Uniport studies. We aimed to unravel the complexity of KRAS and its relationships with other driver mutations. We noticed that G12D and G12V are the prevalent mutated variants of KRAS and coexist with the TP53 mutation in PAAD and CRAD, while G12C and G12V coexist with LUAD. We also noticed similar observations in the case of PIK3CA and APC mutations in CRAD. At the transcript level, a positive correlation exists between KRAS and PIK3CA and between APC and KRAS in CRAD. The existence of the co-mutation of KRAS and other driver mutations could influence the signaling pathway in the neoplastic transformation. Moreover, it has immense prognostic and predictive implications, which could help in better therapeutic management to treat cancer.

Publisher

MDPI AG

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