Distribution of single nucleotide variant (SNV) counts detected through exome sequencing of melanoma samples, grouped by the presence of R alleles of the MC1R locus shown as a boxplot with median, quartiles, whiskers and outliers.

For the first time, researchers at the Wellcome Trust Sanger Institute and University of Leeds have proved that gene variants associated with red hair, pale skin and freckles are linked to a higher number of genetic mutations in skin cancers. The burden of mutations associated with these variants is comparable to an extra 21 years of sun exposure in people without this variant.

The research showed that even a single copy of a red hair-associated MC1R gene variant increased the number of mutations in melanoma skin cancer; the most serious form of skin cancer. Many non-red haired people carry these common variants and the study shows that everyone needs to be careful about sun exposure.

Red-headed people make up between one and two percent of the world’s population but about 6 per cent of the UK population. They have two copies of a variant of the MC1R gene which affects the type of melanin pigment they produce, leading to red hair, freckles, pale skin and a strong tendency to burn in the sun.

“It has been known for a while that a person with red hair has an increased likelihood of developing skin cancer, but this is the first time that the gene has been proven to be associated with skin cancers with more mutations.’

‘Unexpectedly, we also showed that people with only a single copy of the gene variant still have a much higher number of tumour mutations than the rest of the population.  This is one of the first examples of a common genetic profile having a large impact on a cancer genome and could help better identify people at higher risk of developing skin cancer.”

Dr David Adams, joint lead researcher at the Wellcome Trust Sanger Institute
The researchers analysed publically available data-sets of tumour DNA sequences collected from more than 400 people. They found an average of 42 per cent more sun-associated mutations in tumours from people carrying the gene variant.

“This is the first study to look at how the inherited MC1R gene affects the number of spontaneous mutations in skin cancers and has significant implications for understanding how skin cancers form. It has only been possible due to the large-scale data available. The tumours were sequenced in the USA, from patients all over the world and the data was made freely accessible to all researchers. This study illustrates how important international collaboration and free public access to data-sets is to research.”

Exposure to ultraviolet light from either sunlight or sunbeds causes damage to DNA and it has been thought that the type of skin pigment associated with red-heads could allow more UV to reach the DNA.  While this may be one mechanism of damage, the study also revealed that the MC1R gene variation not only increased the number of spontaneous mutations caused by ultraviolet light, but also raised the level of other mutations in the tumours.  This suggests that biological processes exist in cancer development in people with MC1R variation that are not solely related to ultraviolet light.

“This important research explains why red-haired people have to be so careful about covering up in strong sun. It also underlines that it isn’t just people with red hair who need to protect themselves from too much sun. People who tend to burn rather than tan, or who have fair skin, hair or eyes, or who have freckles or moles are also at higher risk.’

Sanger Institute www.sanger.ac.uk/news/view/red-hair-gene-variant-drives-skin-cancer-mutations

The latest developments in prenatal technology conceived by scientists at the Wayne State University School of Medicine that make it possible to test for genetic disorders a little more than one month into pregnancy were revealed.
In the article, the WSU researchers wrote that their non-invasive testing method – Trophoblast Retrieval and Isolation from the Cervix (TRIC) – offers the accuracy of more invasive tests, such as the needle-directed amniocentesis, and can also be utilized five to 10 weeks earlier than current testing modalities.
TRIC was first publicized in 2014 in studies led by principal investigator and Professor of Obstetrics and Gynecology D. Randall Armant, Ph.D. The method isolates several hundred foetal cells that migrate from the placenta into the uterus using a retrieval technique akin to the common Pap smear, and can be done as early as five weeks into pregnancy.
Armant’s co-principal investigator in the latest research is Associate Professor of Obstetrics and Gynecology Sascha Drewlo, Ph.D., who joined the team in 2014 to provide expertise in molecular biology and perinatal medicine.

A related paper published by the two “Altered Biomarkers in Trophoblast Cells Obtained Noninvasively Prior to Clinical Manifestation of Perinatal Disease,” describes the correlation between the levels of certain proteins in the foetal cells isolated by TRIC during the first trimester and the development of intrauterine growth restriction, which results in a small, undernourished foetus in the womb, or preeclampsia – hypertension and kidney disorder of the mother – in the last trimester.

“This finding suggests that it might one day be possible to test these protein levels to identify pregnancies at risk for complications. Such a test could help physicians to better manage the health of mother and baby, and would streamline research on new interventions to prevent or limit the effects of disease,” Armant said.

The paper demonstrates the researchers’ ability to isolate foetal DNA from the cells obtained by TRIC. Since the placenta is derived from the embryo and its DNA is the same as that of the foetus, the researchers can use cells obtained by TRIC for prenatal genetic testing. The paper was co-first authored by Chandni Jain, Ph.D., and Leena Kadam, working in the laboratories of Armant and Drewlo.
“We sequenced the foetal DNA and compared it to that of the mothers, proving that they were different, but the foetal DNA always contained one copy of the mother’s DNA genes. We also had some DNA from the placenta and found that it was identical to the foetal DNA,” Armant said.

The sequencing was completed in 20 consecutive pregnancies collected at five to 19 weeks, with minimal maternal DNA contamination.

Wayne State Universityresearch.wayne.edu/news/studies-reveal-wsu-conceived-non-invasive-prenatal-genetic-test-is-accurate-five-weeks-into-pregnancy-21140

Sysmex Corporation and Siemens Healthcare Laboratory Diagnostics announced on April 13, 2016 an extension to their long-standing partnership through at least 2020. The contract extension adds a minimum of two additional years to the global supply, distributorship, and sales and service agreement for hemostasis products. The partnership enables laboratory customers around the world to continue to benefit from the largest portfolio of hemostasis systems and reagents. The companies, which began collaborating more than 20 years ago, also agreed to continue joint hemostasis product development activities that will streamline and optimize testing in laboratories throughout the world.

Siemens Healthcare and Sysmex provide hemostasis products used to test for blood clotting disorders, preoperative bleeding risk management, and the monitoring of patients on anticoagulant therapy medications. In the past few years alone, the companies have introduced several cutting-edge INNOVANCE reagents and multiple new platforms for various laboratory settings, including the recent worldwide launch of the Sysmex CS-2500 System, and the U.S. launch of the Sysmex CS-5100 System with optional track-based automation.

“We are pleased to extend our longstanding partnership with Siemens Healthcare,” said Hisashi Ietsugu, Chairman and CEO, Sysmex Corporation. “With the aging population, hemostasis testing has become even more important. Our partnership provides our customers with the innovative technologies needed to manage the increase in testing volumes, while providing accurate results for improved patient care.”

“The continued collaboration and twenty-year partnership between Siemens and Sysmex is rare in the rapidly changing world of diagnostics,” said Franz Walt, President, Siemens Healthcare Laboratory Diagnostics. “As a leader in hemostasis testing, our combined mission to offer best-in-class solutions has enabled us to meet the needs of diverse laboratories throughout the world.”

 www.siemens.com

Not only is breast cancer more than one disease, but a single breast cancer tumour can vary within itself, a finding that University of Pittsburgh Cancer Institute (UPCI) researchers discovered has the potential to lead to very different patient treatment plans depending on the tumour sample and diagnostic testing used.

The results demonstrate that tumour sampling techniques used with newly developed “personalized medicine” gene expression profile tests may need to be refined to ensure that the most appropriate tumour sections are selected for testing.

“These tests are a good thing—they’ve done an incredible job identifying women with breast cancers that have a low risk of recurrence who don’t need chemotherapy, saving them from the toxicity and discomfort of unnecessary treatment,” said Adrian V. Lee, Ph.D., professor of pharmacology and chemical biology at UPCI, partner with UPMC CancerCenter. “However, as with any new technology, we need to understand how these tests work, and we’re finding that the sampling process, which involves liquefying tumours, loses information that could be important in determining the best treatment plan for patients with more aggressive tumours.”

Gene expression profiling is an increasingly popular type of test that tells doctors what certain genes are doing in a tissue sample, such as causing the cells to actively divide and multiply. Several tests have been developed in recent years to aid oncologists in developing breast cancer treatment plans. They involve taking a small bit of the tumour—or multiple small bits mixed together—and testing it.

The tests can tell oncologists if the cancer has a low, intermediate or high risk of recurring. The level of risk can help doctors and patients decide whether an aggressive treatment plan involving chemotherapy is beneficial or likely to do more harm than good.

Dr. Lee and his team examined 71 cases of a type of breast cancer called “estrogen-receptor-positive” that was caught early and hadn’t yet spread to other parts of the body. In all cases, the tumour had been removed and samples taken for gene expression profiling. A total of 181 samples were taken from various parts of the tumours, and the researchers measured the expression of 141 different genes from five different types of gene expression profile tests commonly used for breast cancer tumours.

For 25 percent of the patients, their tumours received a different risk of recurrence score depending on which sample was processed.

“This indicates that one part of the tumour is more aggressive than another part. If an oncologist were to know this, he or she would likely recommend a treatment plan tailored to destroy the most aggressive section of the tumour,” said Dr. Lee.

Because the patients in this study were all caught early, their risk of recurrence was low to begin with, and there weren’t enough recurrences to make a meaningful determination on whether they would have done better if more samples were tested from their tumours.

“It would be valuable to repeat this study with a much larger group of breast cancer patients and follow them over time so that we could definitively determine if the way sampling is done with these tests is, indeed, resulting in patients getting cancer recurrences that wouldn’t have happened if the sampling process was changed,” said Dr. Lee.

University of Pittsburgh Cancer Institute

www.upmc.com/media/NewsReleases/2016/Pages/lee-tumorhetero-gep-cancerresearch.aspx

Irritable bowel syndrome (IBS) affects a large portion of the general population. New research coordinated by Karolinska Institutet now shows a link between defective sucrase-isomaltase gene variants and IBS.
Irritable bowel syndrome (IBS) is the most common gastrointestinal disorder. More than 10% of the population suffer from recurrent symptoms including abdominal pain, gas, diarrhoea and constipation. What causes IBS is largely unknown, and this hampers the development of effective treatment for many patients.

Now an international research team led by scientists from Karolinska Institutet in Sweden have identified defective sucrase-isomaltase gene variants that increase the risk of IBS.
“People with IBS often connect their symptoms to certain foods, particularly fermentable carbohydrates. We tested the hypothesis that genetic changes in the breakdown of disaccharides – small carbohydrates from sugars and starches – may be associated with increased risk of IBS,” says corresponding author Mauro D’Amato from Karolinska Institutet.

The researchers studied DNA variants in the gene encoding the enzyme sucrase-isomaltase (SI), due to the observation that SI mutations are often found in hereditary forms of sucrose intolerance, whose main characteristics diarrhoea, abdominal pain and bloating are also common in IBS.

By screening 1887 study participants from multiple centres in Sweden, Italy and US, they found that rare defective SI mutations were twice more common among IBS cases than healthy controls, and a common variant with reduced enzymatic activity was also associated with increased risk of IBS.

“A significant decrease in the enzymatic activity of sucrase-isomaltase would be compatible with poor carbohydrate digestion in the intestine, possibly leading to mal-absorption and bowel symptoms” says co-senior author Hassan Naim from the University of Veterinary Medicine Hannover.
“Our results provide rationale for novel nutrigenetic studies in IBS, with potential for personalizing treatment options based on SI genotype” adds Mauro D’Amato.

Karolinska Institute ki.se/en/news/new-research-links-genetic-defects-in-carbohydrate-digestion-to-irritable-bowel-syndrome