Copy Number Alterations in Enzyme-Coding and Cancer-Causing Genes Reprogram Tumor Metabolism

Area of Science:

• Genomics
• Cancer Biology
• Metabolic Engineering

Background:

• Somatic copy number alterations are common in cancer genomes.
• These alterations can deregulate tumor cell metabolism.
• Metabolic and cancer-associated genes are often found near each other on chromosomes.

Purpose of the Study:

• To identify novel metabolic genes involved in cancer.
• To understand the impact of copy number alterations on cancer metabolism.
• To develop a method for classifying tumors based on metabolic gene profiles.

Main Methods:

• Developed the Identification of Metabolic Cancer Genes (iMetCG) pipeline.
• Analyzed copy number alterations across 19 cancer types from The Cancer Genome Atlas.
• Validated identified genes using gene essentiality, survival data, and overlap with known cancer-metabolic genes.

Main Results:

• Identified 119 novel metabolic cancer genes.
• Found that proximity of metabolic and cancer genes on chromosomes is a common mechanism for metabolic reprogramming.
• Demonstrated that these genes can classify tumors by origin and predict patient survival.
• Validated findings through gene essentiality and overlap with known cancer-metabolic genes.

Conclusions:

• Discovered a new mechanism of metabolic reprogramming in cancer driven by gene proximity.
• Identified a set of novel metabolic cancer genes crucial for rewiring cancer metabolism.
• These findings offer new avenues for cancer classification and therapeutic strategies.