Academic research community (GECIP)

The histopathology of renal tumours is recognised to be increasingly complex. Our understanding of the genetic basis of some of the rarer tumours has advanced in recent years and there are recognised to be morphological correlates to these genetic aberrations. It is also recognised that the histopathologist may be the key to recognising the potential of an undiagnosed underlying hereditary predisposition to a syndrome associated with a renal tumour. However hereditary renal tumours are very rare, representing up to 4% of all renal tumours, and many pathologists are unlikely therefore to encounter such a tumour in routine diagnostic practice. The 100 000 genomes project provides a unique opportunity to explore the morphological correlates of the tumours identified as having an underlying associated hereditary syndrome. Whilst these may already be recognised, it is an opportunity to determine whether there are recurrent themes in terms of morphology that may not yet be recognised and to document these for the pathology community. Furthermore, with access to original pathology reports it will be possible to identify any potential areas of diagnostic challenge, recognition of which may lead, through education, to improvements in the diagnosis of such tumours in the future. For the purpose of this project the requirements would be access to the histology report, pathology slides, and the germline mutation status of the tumours.

Immunotherapy has emerged as a breakthrough form of new cancer treatment, leading to extended survival in a considerable number of patients. However in some patients immunotherapy is not effective, and other treatment options may be more beneficial. Predictive tests are urgently needed to identify which patients will and won’t benefit from immunotherapy treatment, and in this project we will investigate whole genome sequencing data as a potential tool to make these predictions.

Renal cell carcinomas (RCC) originate from the renal epithelium and account for the majority of kidney cancers. Whilst our understanding of RCC has improved over recent years, approximately half of those diagnosed die from the disease. Analysis of how the genetic variants within RCC tumours influence the wider biological environment within that patient, particularly how their immune system responds to the cancerous growth, will help optimise treatment.

Our research looks to uncover what are the genetic factors that make some individuals susceptible to developing kidney and/or neuroendocrine tumours such as phaeochromocytoma or paraganglioma. With this information we will be able to better identify those at risk and develop apropriate cancer prevention strategies

Renal cell carcinomas (RCC) originate from the renal epithelium and account for the majority of kidney cancers. Whilst our understanding of RCC has improved over recent years, approximately half of those diagnosed die from the disease. Analysis of whole genome sequencing data from RCC patients will allow us to identify genetic alterations, molecular pathways and mutational processes key to RCC development and procession, and inform on measures for prevention and treatment of the cancer.

We have learned much about bladder cancer from 'conventional' methods to 'sequence' the genetic code ('DNA'). These efforts have demonstrated the types of DNA changes that underlie bladder cancer ('variants') and in which genes these variants occur. However, there is still a lot that we don't know about how these variants can impact on an individual patient's chances of the disease returning following treatment ('recurrence'), and we know very little about the long pieces of DNA between the genes ('non-coding DNA'). This project aims to investigate the known common DNA variants and non-coding DNA, and their relationship to recurrence and survival from bladder cancer.

Congenital (present-at-birth) anomalies of the kidney and urinary tract account for up to 50% of childhood chronic kidney disease and can often be caused by gene changes. This project will look in detail at the different types of kidney, ureter and bladder malformations and match them with gene sequencing data to understand the changes responsible. This will not only help diagnosis of participants in the project but may also reveal mechanisms that are important in kidney development and disease.

Whilst the treatment options for renal cell carcinoma have expanded, their application in the clinic remain imprecise. This may, in part, underpin why long term responses are seen only in a minority. There is an urgent need for predictive tests to identify which patients will likely respond to which treatment, minimising the risk of untoward & unnecessary side effects whilst maximising the chance of success. This proposal seeks to use Whole Genome Sequencing as a tool to identify predictors of treatment success or failure.