Raunak Shrestha

• Tumor suppressor genes (TSGs), as their inhibit tumor development; if both copies of the gene receive inactivating mutations, the suppressive action is switched off and tumor growth is promoted.

• Oncogenes promote cancer growth when sufficient signal is achieved.

• Haploinsufficiency describes a genetic relationship in a diploid organism in which loss of one copy of a gene causes a phenotype.

• The converse is triplosensitivity, in which an additional copy of a gene produces a phenotype.

OG TSG Neutral Gene

50 50 10917

CGCdatabase

Training Set

PolyPhen2

HiFI LoFI

High Functional Impact

Low Functional Impact

Silent mutations/kb*

Total N Missense mutations

Total N LOF mutations

Total N of Splicing mutations

Missense mutations/kb*

LOF mutations/kb*

Entropy score for missense mutations

LOF/Silent ratio

Splicing/Silent ratio

Missense/Silent ratio

HiFi missense/LoFI missense ratio

LOF/Benign ratio

Splicing/Benign ratio

Missense/Benign ratio

HiFi missense/Benign ratio

Average PolyPhen2 score for missense

LOF/Total Mutations

Missense/Total Mutations

Splicing/Total Mutations

LOF/Missense mutations

High-level Deletion frequency

High-level Amplification frequency

22 Features

Training Set

OG TSGNeutral Gene

50 50 10917

CGCdatabase

Tumor Suppressor and Oncogene Explorer (TUSON Explorer)

General Properties of Cancer Drivers

A Continuum of Cancer Driver Genes

An Unusually High Concentration of TSGs on the X Chromosome

Distribution and Potency of Cancer Drivers on Chromosomes Predict Arm and Chromosome SCNA Frequencies

Distribution and Potency of Cancer Drivers on Chromosomes Predict Arm and Chromosome SCNA Frequencies

Distribution and Potency of Cancer Drivers on Chromosomes Predict Arm and Chromosome SCNA Frequencies

Models of Cancer Evolution

Models of Cancer Evolution