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Table 3 Inference of biological classification by structural effect of mutational landscape

From: DOTS-Finder: a comprehensive tool for assessing driver genes in cancer genomes

   Structural landscape
  Missense Clustered No Clustered Any
  Truncating No Diffuse Diffuse Clustered
Biological classification Oncogene Typical (gain-of-function) for example, KRAS None found None found Atypical (gain of function through loss of inhibition) for example, NPM1
Tumor suppressor Atypical (dominant negative, gain-of-function) Typical (loss-of-function) Atypical (possible dominant negative, gain-of-function*) None found
for example, SMARCA4 in lymphoma for example, RB1 for example, TP53 in UCEC or DNMT3A in AML
  1. Inferring the biological role of OGs and TSGs in cancer via the mutational landscape can lead to borderline results in the classification. While for the majority of known cancer genes there is a clear correspondence between the mutational landscape and the biological classification, other genes require a careful evaluation to assess their functional characteristics (Figure 4).
  2. *A mixed mutational landscape with diffuse truncating and clustered missense in the same tumor type must be carefully analyzed. We should understand whether truncating and missense mutations are mutually exclusive and what is the allelic status (heterozygosity or homozygosity) of the two different patterns.