Mutational signatures efficiently identify different mutational processes underlying cancers with similar somatic...

Area of Science:

• Oncology
• Genetics
• Cancer Research

Background:

• Mutational signatures offer higher resolution for biological processes generating somatic mutations than conventional spectra.
• Previous studies comparing bladder urothelial cancer (BLCA) and cervical squamous cell carcinoma (CESC) mutational signatures did not differentiate underlying mutational processes.
• This limitation reduced the capability of mutational signatures to distinguish between BLCA and CESC.

Purpose of the Study:

• To decipher and compare mutational signatures of BLCA and CESC.
• To identify similarities and differences in mutational processes between these two cancer types.
• To elucidate the roles of endogenous and exogenous carcinogens in somatic mutation generation.

Main Methods:

• Deciphered four mutational signatures from 37,098 somatic mutations in 130 BLCA exomes.
• Deciphered five mutational signatures from 44,206 somatic mutations in 194 CESC exomes.
• Compared the deciphered mutational signatures between BLCA and CESC.

Main Results:

• Identified three highly similar mutational signatures between BLCA and CESC, indicating common endogenous mutational processes.
• Revealed the role of viral infection in both cancers through respective mutational signature 4.
• Discovered a novel CESC-specific mutational signature 4 not previously described.

Conclusions:

• Demonstrated similarities and differences between BLCA and CESC by deciphering mutational signatures.
• Highlighted common endogenous mutational processes and the role of viral infection in both cancers.
• Provided insights into using mutational signatures to clarify mechanisms of carcinogens causing somatic mutations in human cancers.