Genetic and Chromosomal Aberrations and Their Clinical Significance in Renal Neoplasms.

Ning Yi Yap,Ahmad Fadzli,Retnagowri Rajandram,Jayalakshmi Pailoor,Keng Lim Ng,Glenda Carolyn Gobe

doi:10.1155/2015/476508

Abstract

The most common form of malignant renal neoplasms is renal cell carcinoma (RCC), which is classified into several different subtypes based on the histomorphological features. However, overlaps in these characteristics may present difficulties in the accurate diagnosis of these subtypes, which have different clinical outcomes. Genomic and molecular studies have revealed unique genetic aberrations in each subtype. Knowledge of these genetic changes in hereditary and sporadic renal neoplasms has given an insight into the various proteins and signalling pathways involved in tumour formation and progression. In this review, the genetic aberrations characteristic to each renal neoplasm subtype are evaluated along with the associated protein products and affected pathways. The potential applications of these genetic aberrations and proteins as diagnostic tools, prognostic markers, or therapeutic targets are also assessed.

Highlights

The incidence of kidney cancers has been increasing steadily in developed countries over the past decade and new reports show similar trends in developing countries [1,2,3]
Genes involved in the pathway, consisting of MTOR, PTEN, PIK3CA, AKT2, and others, have alterations in 26–28% of clear cell RCC (ccRCC) tumours [106, 123]. These findings provide concrete evidence on the genetic changes directly associated with the PI3K-AKTmTOR pathway in ccRCC
Renal tumours of different histologies such as ccRCC, Papillary Renal Cell Carcinoma (pRCC), Chromophobe Renal Cell Carcinoma (chRCC), and oncocytoma have been reported in BHD sufferers with chRCC and oncocytomas being the predominant types [204]

Summary

Introduction

The incidence of kidney cancers has been increasing steadily in developed countries over the past decade and new reports show similar trends in developing countries [1,2,3]. The most common and characteristic genetic changes in ccRCCs are aberrations such as LOH, hypermethylation, or mutation in 3p chromosome region, which are found in up to 91% of the tumours [15,16,17]. Low ARID1A mRNA and BAF250a (protein product of ARID1A) levels correlated with higher stage, grade, and worse prognosis while SETD2 mutation was associated with worse disease specific survival [93, 105, 111].

Results

Conclusion