Extensive protein dosage compensation in aneuploid human cancers

Area of Science:

• Genomics
• Proteomics
• Cancer Biology

Background:

• Aneuploidy, an abnormal chromosome number, is common in human cancers.
• Its impact on cancer protein expression and the underlying regulatory mechanisms are not fully understood.

Purpose of the Study:

• To investigate how changes in chromosome copy number affect the cancer proteome.
• To identify factors and gene groups involved in buffering protein expression changes.

Main Methods:

• Analysis of matched copy number, RNA expression, and protein expression data from human cancer cell lines and tumors.
• Identification of gene groups and regulatory mechanisms responsible for dosage compensation.

Main Results:

• Most proteins exhibit dosage compensation, resisting changes expected from chromosome copy number alterations alone.
• Specific gene groups, including protein complex subunits and cell cycle genes, are recurrently buffered.
• Genetic and biophysical factors predict protein buffering, indicating complex post-translational regulation.
• Chromosomal aneuploidy has a moderate effect on oncogene and tumor suppressor expression due to dosage compensation.

Conclusions:

• Cancer cells employ sophisticated regulatory mechanisms to maintain protein dosage homeostasis despite aneuploidy.
• Understanding aneuploidy and dosage compensation is crucial for identifying cancer driver genes and therapeutic targets.