Related Experiment Video

Updated: Jun 24, 2026

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
11:15

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors

Published on: September 20, 2016

Thymidylate synthetase allelic imbalance in clear cell renal carcinoma

Davide Colavito1, Giuseppe Cartei, Massimo Dal Bianco

  • 1Research and Innovation S.p.A., Via Svizzera 16, Padua 35127, Italy. microarray@researchinnovation.com

Cancer Chemotherapy and Pharmacology
|March 24, 2009
PubMed
Abstract

Insights

This study reveals loss of chromosome regions 18p11.32 and 18p11.31 in renal cell carcinoma (RCC). These thymidylate synthetase (TYMS) gene allelic imbalances may impact 5-fluorouracil (5-FU) treatment response in advanced RCC patients.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacogenomics

Background:

  • The thymidylate synthetase (TYMS) gene is crucial for 5-fluorouracil (5-FU) chemotherapy efficacy.
  • TYMS variants, like the VNTR in the 5'-untranslated region, are being investigated to personalize 5-FU treatment.
  • No data existed on TYMS allele frequency alterations in renal cell carcinoma (RCC).

Purpose of the Study:

  • To investigate the allelic status of the TYMS gene at chromosome band 18p11.32 in renal cell carcinoma.
  • To determine if TYMS gene variants influence treatment response in advanced RCC.

Main Methods:

  • Collected blood and tumor samples from 41 clear cell RCC patients.
  • Determined TYMS VNTR genotype using PCR and fragment analysis in heterozygotes.
  • Confirmed allelic imbalance using microsatellite markers D18S59 and D18S476 at 18p11.32 and 18p11.31.

Main Results:

  • Germ-line TYMS VNTR distribution showed variations: 2R/2R (19.5%), 2R/3R (36.6%), and 3R/3R (43.9%).
  • Allelic imbalance of the TYMS tandem repeat region was found in 26.6% of heterozygote patients.
  • Overall allelic imbalance was 35% for 18p11.32 and 28% for 18p11.31.

Conclusions:

  • This study provides the first evidence of 18p11.32 and 18p11.31 loss in renal cell carcinomas.
  • Allelic imbalances at the TYMS locus may significantly affect 5-FU responsiveness.
  • Findings may help explain variable patient responses to fluoropyrimidine-based chemotherapies in advanced RCC.

More Related Videos

Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane05:36

Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane

Published on: February 8, 2020

Comparative Lesions Analysis Through a Targeted Sequencing Approach08:16

Comparative Lesions Analysis Through a Targeted Sequencing Approach

Published on: November 5, 2019

Related Concept Videos

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...