Complete response to neoadjuvant chemoradiotherapy in rectal cancer is associated with RAS/AKT mutations and high tumour mutational burden.

Stockton, Joanne D, Tee, Louise, Whalley, Celina, James, Jonathan, Dilworth, Mark P, Wheat, Rachel, Nieto, Thomas, Geh, Ian, Barros-Silva, João D and Beggs, Andrew D (2021) Complete response to neoadjuvant chemoradiotherapy in rectal cancer is associated with RAS/AKT mutations and high tumour mutational burden. Radiation oncology (London, England), 16 (1). p. 129. ISSN 1748-717X.

Full text not available from this repository.
Official URL: 10.1186/s13014-021-01853-y.

Abstract

BACKGROUND

Pathological complete response (pathCR) in rectal cancer is beneficial, as up to 75% of patients do not experience regrowth of the primary tumour, but it is poorly understood. We hypothesised that the changes seen in the pre-treatment biopsies of pathCR but not seen in residual tumour after chemoradiotherapy were the determinants of responsiveness.

METHODS

Two groups of patients with either complete response (pathCR group, N = 24) or no response (poor response group, N = 24) were retrieved. Pre-treatment biopsies of cancers from these patients underwent high read depth amplicon sequencing for a targeted panel, exome sequencing, methylation profiling and immunohistochemistry for DNA repair pathway proteins.

RESULTS

Twenty four patients who underwent pathCR and twenty-four who underwent poor response underwent molecular characterisation. Patients in the pathCR group had significantly higher tumour mutational burden and neoantigen load, frequent copy number alterations but fewer structural variants and enrichment for driver mutations in the PI3K/AKT/mTOR signalling pathway. There were no significant differences in tumour heterogeneity as measured by MATH score. Methylation analysis demonstrated enrichment for hypomethyation in the PI3K/AKT/mTOR signalling pathway.

DISCUSSION

The phenomenon of pathCR in rectal cancer may be related to immunovisibility caused by a high tumour mutational burden phenotype. Potential therapy resistance mechanisms involve the PI3K/AKT/mTOR signalling pathway, but tumour heterogeneity does not seem to play a role in resistance.

Item Type: Article
Subjects: QZ Pathology. Oncology
Divisions: Planned IP Care > Oncology and Clinical Haematology
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Depositing User: Miss Emily Johnson
Date Deposited: 16 Jul 2021 13:48
Last Modified: 16 Jul 2021 13:48
URI: http://www.repository.uhblibrary.co.uk/id/eprint/4493

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