Skip to content

Patterns of somatic mutation in human cancer genomes #
Find similar titles

Summary #

Introduction #

driver and passenger mutations을 구분하는 것은 도전이다.

The aim of these studies was to survey the numbers and patterns of somatic point mutations in a diverse set of human cancer genomes and hence to obtain insights into the relative contributions of driver and passenger mutations.

Somatic protein kinase mutations #

kinase 유전자 패밀리는 암 유전자인 경우가 많으며, 이들 유전자의 저해제가 암 치료제인 경우가 많다.

각종 암 210에서 kinase 유전자들(518) 코딩영역과 splice junction을 시퀀싱 - 274 Mb - 1007 somatic mutation을 찾다.

Prevalence of somatic mutations #

많은 것부터 없는 것까지 다양

Signatures of somatic mutations #

암종에 따라 다른 특징

Prevalence of driver and passenger mutations #

Germline polymorphism에 C:G>G:C는 별로 없는데, 몇몇 암종에는 많이 발견됨

Characteristics of driver mutations #

driver냐 아니냐 확인 - observed ratio of non-synonymous: synonymous mutations compared with that expected by chance --> positive or negative selection

158 drivers, 921 passengers 확인

MMR deficent cancer는 selective pressure가 낮음 (1.08) - 변이율이 올라가면 전체적으로 선택압은 낮아진다.

kinase 관련 변이와 아닌 것과의 pressure 차이는 1.4:1.23

Potential protein kinase cancer genes #

selection pressure로 driver 정도를 정렬하여 보면, 잘 알려진 암 유전자들도 있고, 그렇지 않은 것들도 있음.

Reactome, Panther, INOH 데이터셋을 이용한 pathway 분석시, FGF signalling pathway가 가장 유의하게 높게 나옴.

재미있게도 Apoptosis나, Cell cycle 관련 pathway는 나오지 않음.

Discussion #

518중 120개 유전자가 driver mutation으로 보임.

Methods #

DNA from primary tumors, cancer cell lines, normal tissue samples. More than 80% of tumour cells were used.

To assess the significance of this ratio, an exact Monte Carlo test was developed which was applied to the entire set and to subsets of mutations.

Suggested Pages #