Biomarker-driven oncology therapeutics and whole genome cancer sequencing: an executive summary

by | Jan 26, 2024 | Executive Summary

Research article - Nature Medicine

Results from the UK 100,000 Genomes Project are reported in a paper in Nature Medicine. Genomics England, alongside NHS England, analyzed whole genome-sequencing (WGS) data from 13,880 solid tumors spanning 33 cancer types – the objective being to integrate genomic data with real-world treatment and outcomes from national clinical databases.

A high percentage of cases had one or more clinically relevant somatic mutations present in genes indicated in the National Genomic Test Directory for Cancer. Most commonly these were:

  • glioblastoma multiforme (95%),
  • low-grade glioma (93%),
  • skin cutaneous melanoma (74%),
  • head and neck squamous cell carcinoma (71%),
  • colon and rectal adenocarcinoma (69%), and
  • lung adenocarcinoma (68%).

Frequently mutated gene – TP53

The most frequently mutated gene was TP53 – occurring in 39.0% of patients overall and being most frequent (more than 70% of cases) in uterine corpus endometrial serous carcinoma, ovarian high-grade serous carcinoma, lung squamous cell carcinoma, rectum adenocarcinoma, esophageal adenocarcinoma and esophageal squamous cell carcinoma. Tumor mutational burden was also analysed and, consistent with the published literature was found to be highest in skin cutaneous melanoma and lung adenocarcinoma.

Gene affecting patient outcome – CDKN2Ae

CDKN2A was the gene which affected patient outcome most severely – being associated with high-grade disease and poor prognosis in some cancer subtypes (e.g. glioma and soft-tissue sarcoma).

The results were also consistent with well-established poor-prognostic indicators, such as KRAS mutants in colorectal cancer and non-small cell lung cancer or TP53 mutations in non-small cell lung cancer.


The paper demonstrates the value of linking genomic and real-world data to optimise cancer care, by identifying clinically actionable mutations to select precision medicine for individual patients. Additionally, providing opportunities to select patients for clinical research to allow the development of new medicines.

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Sosinsky A, Ambrose J, Cross W, Turnbull C, Henderson S, Jones L, et al. (2024). Insights for precision oncology from the integration of genomic and clinical data of 13,880 tumors from the 100,000 Genomes Cancer Programme. Nature Medicine. 30(1):279–89. Available from: