Tumor Evolution - Simplicity and Constraints

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Compares 42 tumors from 6 patients using whole-genome 40x plus deep exomes 150–200x, mutation calling and copy‑number analysis against TCGA. Finds 3p loss in nearly all tumors but one patient shows 3q loss in 10/13 tumors (p extremely small), strong patient-specific mutational spectra biases, and many low‑grade tumors carry only clonal VHL with additional drivers appearing subclonally; deep exomes recover some missed drivers but large fractions of tumors still lack known drivers, raising mechanistic questions.

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1. 0:00Intro
2. 0:30Familial clear cell RCC project
3. 6:26Sequenced 42 tumors from 6 patients (6 blood + 3 adjacent normal controls)
4. 8:34The number of mutations per tumor are positively correlated with age.
5. 9:20Mutation Number not Correlated with Smoking
6. 11:07Vast Majority of Mutations are Private to One Tumor
7. 13:45Mutation type frequencies across patients
8. 16:11Tumors from the Same Patient Have More Similar Mutation Spectra
9. 16:33Random Permutation of Tree is Highly Significant (5 in 100,00 permutations)
10. 17:08Copy Number in 551 TCGA CCRCC Tumors Chromosomes
11. 18:55Copy Number in VHL Tumors Chromosomes
12. 21:24No Evidence of Shared Mutations
13. 29:19Genetic Intratumor Heterogeneity and Phylogeny in Patient 1.
14. 30:17Evidence for Linear Evolution in hereditary
15. 30:54Branched vs Linear Evolution
16. 34:31Let's Think About Size 158 mutation
17. 36:40How Can Tumors Have so Few Drivers?
18. 37:12Abnormalities in Papillary Kidney
19. 38:20Many Cases with no Drivers
20. 39:17Acknowledgements