An international multi-centre research effort has identified a new genetic defect as a potential heritable breast cancer susceptibility candidate. The same PALB2 mutation also seems to in some measure cause prostate cancer.
Cancer is a complex and common disease caused by a combination of both genetic and environmental factors. An inherited predisposition seems to be involved in at least 5–10 per cent of all cases of breast cancer. The two major familial breast cancer susceptibility genes BRCA1 and BRCA2 only explain 20-30 per cent of families with site-specific female breast cancer, which suggests the contribution of additional susceptibility genes. According to Dr Robert Winqvist, who coordinates the research effort, the identification of these genes may help to clarify the genetic background contributing to breast cancer and suggest novel pharmaceutical targets. It could also lead to genetic screening that identifies individuals at increased breast cancer risk and result in improved prevention efforts and treatment.
About a year ago, Dr Bing Xia and Professor David Livingston at the Dana-Farber Cancer Institute in Boston identified a novel BRCA2 binding factor, PALB2 that regulates certain key functions of normal BRCA2 activity. The next step was to set out to evaluate the newly detected PALB2 gene as a potential heritable breast cancer susceptibility candidate by screening for disease-related alterations. The results of this international research effort were recently published in Nature.
The research first involved comprehensive screening for genetic aberrations in 113 Finnish breast cancer families. The same constitutional mutation in PALB2 was observed in three families. It was later showed that the relevant mutant protein is deficient in its ability to support the kinds of DNA damage responses in which PALB2 normally participates. The mutation was further also investigated in 1,918 specimens from an unselected series of Finnish breast cancer individuals. This study revealed 18 mutation-positive individuals, about one per cent of the studied patients, most of whom turned out to have a familial pattern of disease development. The study also involved 141 unselected male breast cancer patients, 188 familial and 288 unselected colorectal cancers, as well as 164 familial and 475 unselected prostate cancer patients. In prostate cancer, one multigenerational cancer family was found where cancer occurred in several generations and all patients showed the single mutation in PALB2 that was studied. According to Winqvist, this suggests that this Finnish founder mutation may be important in heritable prostate cancer as well. Male breast cancer and colorectal cancer cases did not display the mutation.
The constitutional mutation elevates the risk of breast cancer four-fold
"Present results show that the discovered PALB2 mutation elevates the risk of breast cancer four-fold. However, we still need more research to better assess the effect on cancer development. As the comprehensive mutation analysis was originally conducted on only 113 cancer families, it may be that there still are other PALB2 genetic defects accounting for heritable breast and prostate cancer susceptibility. Recent results also imply that PALB2 might be a cancer susceptibility gene in other populations as well. It's been shown that two of the mutations identified in Fanconi anemia patients in non-Finnish populations seem to be associated with familial breast cancer," says Winqvist.
Winqvist points out that, in spite of recent advances, known factors can only explain a fraction of heritable susceptibility to breast cancer. He is nonetheless disposed to believe that the evaluation of yet other biologically significant factors will in time improve the situation. "Hopefully, increased knowledge of underlying mechanisms will provide better conditions for cancer prevention, diagnostics and treatment," Winqvist says.
The multi-centre research involved researchers from Oulu, Tampere, Kuopio and Helsinki Universities or university hospitals in Finland as well as from the US National Cancer Institute. The other research coordinator was Professor David Livingston from Boston. The discovery of the PALB2 genetic mutation was made by HanneleErkko, a PhD student in the Winqvist laboratory, who also carried out a number of the genetic analyses that followed. Dr Xia from the Livingston team was in charge of key analyses to prove the biological significance of the mutation.
The funding bodies behind the research include the Academy of Finland, the Foundation for the Finnish Cancer Institute, the Northern-Ostrobothnia Health Care District and the University of Oulu as well as by the US National Cancer Institute NCI.The article was published in Nature on 8 February.
Niko Rinta | alfa
The balancing act: An enzyme that links endocytosis to membrane recycling
07.12.2016 | National Centre for Biological Sciences
Transforming plant cells from generalists to specialists
07.12.2016 | Duke University
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
07.12.2016 | Health and Medicine
07.12.2016 | Life Sciences
07.12.2016 | Health and Medicine