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International Journal of Molecular Sciences

Solid and blood cancers differ in how one gene is altered

Protein-shortening mutations accounted for 34.2% of samples with the altered gene in solid cancers, versus 24.4% in blood cancers.

Paper by Haichun Huang, Yikui Xie, Baoping Guo, Ying Duan, Hong Cen · Guangxi Medical University Cancer Hospital
Figure 1 from International Journal of Molecular Sciences
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Figure 1. Huang et al., CC BY

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Mechanisms
Studied:
Computational study (64,000 participants, genetic association study, independent replication)

Editor of record: Boris Djordjevic · AgingResearch.News

Paper
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Human cancer datasets covering 10,639 solid tumor samples and 10,042 blood cancer samples formed the basis of a computational observational analysis. Researchers compared mutations in TP53, the gene for p53, a protein that helps suppress tumors. They distinguished mutations expected to eliminate the protein from those expected to leave a full-length altered protein.

Protein-shortening mutations accounted for 34.2% of altered solid tumor samples and 24.4% of altered blood cancer samples. The pattern also appeared in two other databases. The authors proposed that drugs aimed at restoring the altered protein’s activity would make sense where the full-length protein remains.

Why it matters

Cancer is an age-related disease. The authors’ distinction raises a treatment-design question: whether an altered protein remains available for a drug to reactivate.

Caveats

Protein retention in blood cancers was inferred from mutation type, not measured. The proposed strategy of reactivating the altered protein was not tested.

From the paper

Follow-up

… with a median follow-up of 24.0 months among censored patients (this is slightly smaller than the 3684 samples entered into the per-type models because samples without a positive survival time were excluded).

Results, 2.3. What the State Does: Retained-Allele Dose and Loss of the Wild-Type Allele

Result

Counting a sample as truncating whenever any truncating variant was present gave 34.3% in solid and 24.6% in hematologic samples (odds ratio 1.60, 95% CI 1.34–1.89), essentially identical to the severity-ranked rule (34.2% and 24.4%; odds ratio 1.61, 1.35–1.91) …

Results, 2.1. Two States of One Gene, and How They Are Measured

Quoted word for word from the full text on mdpi.com.

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