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Published on: April 11, 2016
Integrating DNA Mutations and RNA Expression of Cancer Driver Genes in Asian Rare Cancers: A Pan-Cancer Analysis
Kathleen Yasmin de Almeida1, Marcelo Severino B Imasa2, Pei Jye Voon3
1Department of International Clinical Development, National Cancer Center Hospital, Tokyo, Japan.
JCO Precision Oncology
|June 29, 2026
Summary
Tumor lineage primarily influences cancer driver gene expression, but specific genomic alterations like TP53 mutations offer crucial clinical insights. Integrative analysis aids precision oncology in rare cancers.
Area of Science:
- Genomics
- Transcriptomics
- Oncology
Background:
- Rare cancers exhibit molecular diversity, complicating treatment decisions.
- The interplay between tumor lineage, somatic alterations, and gene expression in rare cancers is not well understood, especially in Asian populations.
Purpose of the Study:
- To investigate the relative impact of tumor lineage versus DNA mutations on cancer driver gene RNA expression.
- To assess the clinical relevance of genomic alteration status in rare cancers among Asian patients.
Main Methods:
- Integrated DNA and RNA sequencing from 128 rare cancer patients via the MASTER KEY Asia network.
- Elastic net regression identified determinants of RNA expression; findings were validated in a separate cohort.
Main Results:
- Tumor lineage predominantly dictated RNA expression for 17 of 27 driver genes (63%).
- Genomic alterations in ERBB2 or ARID1A correlated with reduced disease progression (P=.01).
- TP53 gain-of-function mutations were linked to increased progression and shorter survival compared to loss-of-function variants (P=.007).
Conclusions:
- Genomic alteration status, including TP53 functional classification, provides vital clinical information beyond transcriptomics.
- Integrative genomics and transcriptomics are essential for advancing precision oncology in rare cancers.
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