Scientists find gene linked to ovarian and breast cancer


Scientists find gene linked to ovarian and breast cancer


Mutations in a gene known as PPM1D are associated with a higher risk of breast and ovarian cancer - which may represent a new cancer-causing process.

The finding came from a new study published in the journal Nature which was conducted by a team of experts from The Institute of Cancer Research, London.

Females with the PPM1D mutations have a 1 in 5 chance of developing either breast or ovarian cancer, which is twice the risk of breast cancer and more than 10 times the risk of ovarian cancer for females in the general population.

A prior study found that mutations in the gene known as RAD51C are associated with a 60 to 80% increased risk for breast cancer and 20 to 40% for ovarian cancer.

According to the authors, the new research suggests that genetic testing and targeted prevention for cancer may be necessary, especially for ovarian, cancer because it is frequently detected at a late stage.

PPM1D appeared to be functioning in an entirely dissimilar way to other genes that are associated with an increased risk of ovarian and breast cancer, including BRCA1 and BRCA2.

Two copies of every gene are found in the human body. In the majority of genes that cause cancer, a mutation in one copy is inherited and found in each cell, while the tumor contains the second mutated copy.

The experts found that in this case, PPM1D mutations were not inherited and were only present in blood cells, instead of every cell. There were no PPM1D mutations found in the normal ovarian or breast cells or in the cancer cells.

PPM1D becomes overactive due to the mutations, which cause a decrease in the action of TP53 - the most common mutated gene in cancer cells.

Professor Nazneen Rahman, head of genetics at The Institute of Cancer Research (ICR), head of the cancer genetics clinical unit at The Royal Marsden NHS Foundation Trust, and research leader, explained:

"This is one of our most interesting and exciting discoveries. At every stage the results were different from the accepted theories. We don't yet know exactly how PPM1D mutations are linked to breast and ovarian cancer, but this finding is stimulating radical new thoughts about the way genes and cancer can be related.

"The results could also be useful in the clinic, particularly for ovarian cancer which is often diagnosed at an advanced stage. If a woman knew she carried a PPM1D mutation and had a one in five chance of developing ovarian cancer, she might consider keyhole surgery to remove her ovaries after completing her family."

Novel sequencing technologies which allow for a much deeper examination of genes were important to the finding. Only some cells had the PPM1D mutations (the so-called mosaic pattern), which is hard to notice with older sequencing techniques.

The researchers pointed out that comparable mosaic mutations in other genes, and in individuals with different kinds of cancers, may potentially appear, as in-depth sequencing research is now being conducted by several experts.

There were 507 genes examined that have a role in DNA repair in 1,150 females with ovarian or breast cancer. Analysis showed that five women had PPM1D gene mutations.

The PPM1D gene was then sequenced in 7,781 female breast or ovarian cancer victims and 5,861 women from the general population. The team found 25 faults in the PPM1D gene in those with cancer and only one in those without, a difference that is statistically notable.

Professor Alan Ashworth, chief executive of The Institute of Cancer Research and one of the study researchers, said:

"This discovery really does turn conventional wisdom about the way genetic mutations can lead to cancer on its head. As we unravel this puzzle, we are likely to gain valuable insights about how cancer develops, and new tools for assessing people's risk of the disease and targeting preventive treatment."

Dr Michael Dunn, Head of Molecular and Physiological Sciences at the Wellcome Trust, added: This study is a fantastic example of the power of next generation sequencing to discover new cancer predisposing genes, offering opportunities for better diagnosis. The discovery also opens up a very exciting new avenue of research in the study of cancer development."

The research received funding from the Wellcome Trust, the ICR, Breakthrough Breast Cancer, and Cancer Research UK.


BRCA mutation (Video Medical And Professional 2018).

Section Issues On Medicine: Disease