Cancer research: Mapping RAS gene mutations based on 60,000 tumors in 51 human cancer types

RAS is one
of the most widespread common oncogenes present in human cancers.

Recently, research teams from Johns Hopkins University School of Medicine, Vanderbilt University Medical Center, and Memorial Sloan Kettering Cancer Center have collaborated to publish an article
titled "Genomic Landscapes and Hallmarks of Mutant RAS in Human Cancers" at Cancer Research 。 To better understand the prevalence of somatic RAS mutations and the genetic profile of co-mutations in RAS mutant tumors, the research team analyzed targeted NGS sequence data from 66,372 tumors involving 51 cancer types in the American Association for Research for Cancer (AACR) project GENIE involving 51 cancer types, estimated the specific prevalence of RAS and non-RAS somatic mutant cancers, and revealed the effect of tumor mutation load and mutation characteristics on
co-mutation patterns.

The article was published in Cancer Research

The research team analyzed targeted NGS data from AACR project GENIE Registry version 6.

The results showed that the median posterior prevalence of RAS codons 12, 13 and 61 mutations varied greatly among different cancer types: pancreatic cancer (PAC) was 74.

Figure 1.

Next, the team adjusted the analysis of prevalence to study differences in the distribution of RAS allele mutations in age, sex, and ethnicity (Figure 2
).

At the same time, the research team evaluated the distribution
of RAS allele mutations in different ethnic backgrounds.

Figure 2.

To assess the genetic profile of RAS co-mutations, the research team used Bayesian models to stratify the dependency relationship between RAS and non-RAS genes (Figure 3).

Figure 3.

Given the differences in the prevalence of RAS allele mutations across ages, sexes, and races, the team concluded that co-mutation patterns may also have a differential distribution in patient subpopulations, and explored this hypothesis through stratified analysis (Figure 4).

Figure 4.

Finally, the research team explored the correlation
between the specific genomic trajectory of RAS mutant tumors and clinical outcomes.

In tumors with co-mutations in KRAS G12C, there were also significant differences
in clinical outcomes among patients treated with immunotherapy.

Figure 5.

Together, the research team's comprehensive assessment of RAS co-mutations revealed background-dependent genomic signatures
of RAS mutant tumors.