Major Lessons from Tumor Sequencing
1. Many mutations — but only a few matter
Tumors can carry thousands of mutations, but only a handful actually “drive” cancer.
Vogelstein compared cancer genomes to mountains (genes frequently mutated across tumors) and hills (genes mutated more rarely).
2. Common pathways, diverse mutations
Even though individual genes differ across tumors, driver mutations cluster into a few biological pathways.
These pathways control essential processes such as cell survival, cell fate, and genome maintenance.
3. Mutation burden varies
Some cancers, like melanoma or lung cancer, have very high mutation rates due to UV or smoking exposure,
while pediatric cancers have far fewer mutations.
4. Tumor evolution and heterogeneity
Sequencing shows that tumors aren’t uniform — they are made up of subclones that evolve over time.
This explains why cancers often relapse or develop resistance to therapy.
5. Unexpected discoveries
Newly identified driver genes affect diverse cellular processes, including chromatin structure,
RNA splicing, and metabolism — revealing new mechanisms of cancer development.
6. Precision medicine potential
Genomic data now guide therapy. Drugs that target specific mutations show how sequencing can
personalize cancer treatment and improve patient outcomes.
Challenges Ahead
Distinguishing driver from passenger mutations remains difficult.
Coping with tumor heterogeneity and turning discoveries into effective treatments are still major hurdles.
Many mutations are also undruggable, limiting current therapeutic options.
Conclusion
Genomic sequencing has transformed cancer research by showing that beneath the apparent chaos of thousands of mutations,
only a small set truly drives tumor growth. These insights have paved the way for precision oncology,
allowing treatments to be tailored to each tumor’s genetic makeup.
📚 Source
Garraway, L. A., & Lander, E. S. (2013). Lessons from the Cancer Genome. Cell, 153(1)