Schulze et al. Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets. Nat Genet. 2015;47:505-511. PMID 25822088

One-paragraph summary

Exome analysis of 243 HCCs mapped recurrent alterations and risk-factor-associated mutational signatures. TERT promoter, CTNNB1, TP53, AXIN1, chromatin-remodeling, oxidative-stress, and growth pathways defined a heterogeneous landscape; roughly 28% of tumors carried a potentially actionable alteration under then-current drug knowledge.

Key findings

• TERT promoter alteration emerged as a common early event.
• CTNNB1 and TP53 anchored major biological groups.
• Alcohol/tobacco and aflatoxin exposures left detectable mutational signatures.
• Common drivers were not readily druggable.

Limitations

• Resected tumors and available tissue create stage/selection bias.
• “Actionable” did not demonstrate HCC clinical benefit.
• Exome data underrepresent epigenetic, transcriptomic, and microenvironmental state.

Why it matters

The study organized HCC genomic heterogeneity while explaining why abundant molecular knowledge had not yet produced a lung-cancer-like targeted-therapy algorithm.

Cited by wiki pages

• overview
• molecular landscape