Mutational Profile of KRAS, NRAS, BRAF, and PIK3CA genes in Ugandan Colorectal Cancer Patients

Wismayer R, Matthews R, Whalley C, Kiwanuka J, Kakembo FE, Thorn S, Wabinga H, Odida M and Tomlinson I

Published on: 2025-07-11

Abstract

Introduction: In the clinical assessment of progression and development of colorectal cancer (CRC), mutations in KRAS, BRAF, PIK3CA, and NRAS genes are critical factors. In Uganda, however, the data regarding the genetic profile of CRC patients is limited except for BRAF and KRAS mutations. The objective of this study was to determine the mutational spectrum of these genes and the association between the clinicopathological features and these mutations in Ugandan CRC patients.

Methodology: To reach these objectives, a total of 127 patients with CRC were recruited between 2008-2021. Mutations in BRAF, KRAS, PIK3CA and NRAS was determined using pyrosequencing and PCR.

Results: BRAF, KRAS, PIK3CA, and NRAS mutations were identified in 3.2%, 6.3%, 29.1% and 2.4% of the cases, respectively. There were some significant correlations between BRAF and PIK3CA mutations and clinicopathological features. Mutations in BRAF were shown to be associated with the SRCC histopathological subtype 4(50%) (p=0.011) and were predominantly found in right sided colon tumours 3(75%) (p=0.023). Whilst PIK3CA mutations were more prevalent in females 23(62.2%) (p=0.012). There was a tendency for PIK3CA mutations to be associated with increasing size of the tumour; T3: 21(56.8%) compared to T1: 3 (8.1%) (p=0.032).

Conclusions: Our study revealed a high PIK3CA mutation rate similar to other studies in the Western world. The BRAF mutation was predominantly found in right sided colon tumours and associated with poor prognostic markers such as small cell colorectal carcinoma. The PIK3CA mutation was associated with larger tumours in Ugandan CRC patients.