Researchers discover genetic risk factor for skin, prostate and brain cancers

September 25, 2011

Scientists at deCODE Genetics and academic collaborators from Iceland, The Netherlands, Spain, Denmark, Germany, Sweden, the USA, the UK and Romania today report the discovery of a variant in the sequence of the human genome associated with risk of developing basal cell carcinoma of the skin (BCC), as well as prostate cancer and glioma, the most serious form of brain cancer. The study was done in collaboration with Illumina, Inc., and is published today in the online edition of Nature Genetics.

Using Illumina sequencing technology, deCODE scientists determined the sequences of the entire genomes of 457 Icelanders, and identified 16 million single (SNPs). Through a combination of SNP genotyping and computational techniques utilizing the extensive Icelandic genealogy, they were able to propagate those 16 million variants into over 40,000 Icelanders for use in this study.

The researchers discovered a single letter variant located in TP53, a gene known to play a central role in and for accumulating so called , during the development of cancer in patients. Until now, however, individuals who are born with defective copies of the gene (germline variants) have been found extremely rarely, only in families with syndromes, Li Fraumeni syndrome (LFS) and Li-Fraumeni-like syndrome (LFL). The variant found in the present study is an unusual type of mutation that appears to affect the way the gene's is processed; the messenger RNA in patients with the mutant TP53 gene appears to lack proper termination and polyadenylation.

This is the first evidence of a germline variant in TP53 associated with cancer predisposition beyond LFS and LFL. While the mutations causing LFS and LFL syndromes are very rare (occuring 1:5)(000 to 1:20)(000 to 1:000 births), the variant described in this paper occurs in ~ 1 in 25 individuals in Iceland, and at comparable frequencies in US and UK populations.

"This mutation is one of a growing number of deCODE discoveries of relatively low frequency sequence variants with large effect," said Kari Stefansson, deCODE's CEO and senior author of the study. "The discovery of such variants is made possible through the breadth and quality of the data that the Icelandic population provides."

Dr. Stefansson emphasized, "We will, together with our collaborators, including Illumina, extend ourselves to turn this discovery into benefit for patients and those at risk of cancer."

BCC is the most common cancer in people of European ancestry. Sun exposure is the primary risk factor for BCC, but genetic predisposition also plays a substantial role. Until now, no mechanistic causal connection between cancers as diverse as BCC, prostate cancer, glioma, and colorectal adenoma was known.

More information: The paper, "A Germline Variant in the TP53 Polyadenylation Signal Confers Cancer Susceptibility" is published online in Nature Genetics at DOI:10.1038/ng.926 and will appear in an upcoming print edition of the journal.

Related Stories

Recommended for you

Scientists provide insight into genetic basis of neuropsychiatric disorders

July 21, 2017
A study by scientists at the Children's Medical Center Research Institute at UT Southwestern (CRI) is providing insight into the genetic basis of neuropsychiatric disorders. In this research, the first mouse model of a mutation ...

Scientists identify new way cells turn off genes

July 19, 2017
Cells have more than one trick up their sleeve for controlling certain genes that regulate fetal growth and development.

South Asian genomes could be boon for disease research, scientists say

July 18, 2017
The Indian subcontinent's massive population is nearing 1.5 billion according to recent accounts. But that population is far from monolithic; it's made up of nearly 5,000 well-defined sub-groups, making the region one of ...

Mutant yeast reveals details of the aberrant genomic machinery of children's high-grade gliomas

July 18, 2017
St. Jude Children's Research Hospital biologists have used engineered yeast cells to discover how a mutation that is frequently found in pediatric brain tumor high-grade glioma triggers a cascade of genomic malfunctions.

Late-breaking mutations may play an important role in autism

July 17, 2017
A study of nearly 6,000 families, combining three genetic sequencing technologies, finds that mutations that occur after conception play an important role in autism. A team led by investigators at Boston Children's Hospital ...

Newly discovered gene variants link innate immunity and Alzheimer's disease

July 17, 2017
Three new gene variants, found in a genome wide association study of Alzheimer's disease (AD), point to the brain's immune cells in the onset of the disorder. These genes encode three proteins that are found in microglia, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.