Study suggests three genes are associated with post-traumatic stress disorder
Three genes involved in serotonin metabolism have been shown to associate with post-traumatic stress disorder.
A study recently published in the Journal of Affective Disorders has suggested that two genes, TPH1 and TPH2, and a common polymorphism region, 5HTTLPR, are associated with the symptoms of post-traumatic stress disorder (PTSD) and depression in individuals who have experienced traumatic events.
Researchers from the University of California (CA, USA) studied multiple generations of 12 families who were affected by the 1988 Spitak earthquake in Armenia.
Two hundred individuals, from up to five generations of a family, were assessed for symptoms of PTSD and depression as well as the severity of their exposure to the trauma.
An association was found between the T alleles of both the TPH1 and TPH2 genes and PTSD symptoms. These genes play an important part in the conversion of tryptophan to serotonin, a neurotransmitter whose activity is linked to mood and sleep regulation.
Armen Goenjian, the lead author of the study says: “We suspect that the gene variants produce less serotonin, predisposing these family members to PTSD after exposure to violence or disaster.”
The third association implicates a polymorphic region of the SLC6A4 gene, 5HTTLPR, as important in altering the risk of developing depressive symptoms. The gene encodes the serotonin transporter, also important in the regulation of serotonin activity.
The researchers postulate that finding genes that relate to PTSD and depression will allow new discoveries in this area of research, by implicating biological mechanisms in the pathology of this disorder that have not been previously elucidated.
Groenjian also envisages other potential uses for these findings. As he explains: “A diagnostic tool based upon TPH1 and TPH2 could enable military leaders to identify soldiers who are at a higher risk of developing PTSD, and reassign their combat duties accordingly.”
In the future, the researchers are looking to see if these findings are true for different racial groups. According to Groenjuan: “Our next step will be to try and replicate the findings in a larger, more heterogeneous population.”
– Written by Alisa Crisp
Source: Goenjian AK, Bailey JN, Walling DP et al. Association of TPH1, TPH2 and 5HTTLPR with PTSD and depressive symptoms. J. Affect. Disord. doi:10.1016/j.jad.2012.02.015 (2012) (Epub ahead of print).
Sequencing technology identifies new approaches for personalizing cancer treatment
Researchers at Washington University (MO, USA) have used a DNA sequencing technology to identify mutations responsible for the development of a patient‘s tumor and also to map the progression of disease, thus monitoring the response to treatment. It is thought that this kind of technique could be of great importance in achieving the goal of personalizing cancer treatment.
The research group, led by Elaine Mardis, has already sequenced the tumor DNA of over 700 cancer patients. In these cases, they compared the tumor DNA with healthy DNA in the same patient, highlighting any mutations that could be responsible for the disease. The findings of these whole-genome sequencing studies have provided evidence for the idea that tumors should be classified by their genetic make-up, rather than by their location in the body. The importance of these kinds of studies is that they identify mutated genes that can be targeted by certain drugs, meaning that a particular cancer patient could receive a form of treatment, tailored specifically to them.
In this particular study, the investigators used ‘deep digital sequencing‘ (a technique developed by the Genome Institute, Washington University) to sequence individual tumor mutations. Each mutation was sequenced over 1000-times. Once these data had been collated, they provided a read-out of the frequency of each tumor mutation in the patients‘ genomes. Using this, the researchers could then map out the genetic progression of the cancer cells in each patient.
Of particular interest, it was observed that although new mutations occur as cancer progresses, each tumor maintained the original cluster of mutations that triggered the disease. This finding was of importance as it suggests that drug therapies should be targeted not only for an individual, but for the mutations present at a particular stage of the disease.
In another study, the same group sequenced the tumors of patients with breast cancer before and after aromatase inhibitor therapy. This led to the identification of genomic changes that occurred in responsive patients compared with those who were unresponsive to the drug. This study indicates that different treatment strategies are probably needed for those patients who do not undergo this genomic change.
Mardis acknowledges that personalizing drug treatments is not easy when it comes to developing new therapies, commenting “Having all treatment options available for every patient doesn‘t fit neatly into the confines of a carefully designed clinical trial. We‘re going to need more flexibility.” However, she is optimistic about what this kind of technology can contribute to individual treatment in diseases such as cancer: “As we move forward, we think sequencing will contribute crucial information to determining the best treatment options for patients.”
– Written by Jonathan Wilkinson
Source: Washington University News Room: https://news.wustl.edu/news/Pages/23644.aspx
General Electric grant awarded to Moffitt researcher‘s mission to offer personalized treatment for metastatic breast cancer
Breast cancer and its associated metastases have received intense research interest, as well as funding and backing from investors. Breast cancer researcher, Catherine Lee and her research team at the Moffitt Cancer Center (FL, USA), whose mission statement is to contribute to the prevention and cure of cancer, are to be awarded a US$100,000 grant to assist in this endeavor. The grant comes from General Electric‘s US$100 million Healthymagination Challenge, which aims to develop genetic tools to investigate the genetic make-up of individuals to determine predisposition or resistance to breast cancer metastasis.
In 2011, an estimated 230,430 women in the USA were diagnosed with breast cancer, of them, approximately 40,000 will not survive from the metastatic spread of the disease. General Electric‘s Healthymagination fund is focused on “finding new ideas that accelerate innovation in early diagnosis, patient stratification and the personalized treatment of breast cancer.”
Lee‘s accepted proposal is based on the identification of a number of specific genes and variations of those genes associated in the development of metastatic breast cancer. Lee believes that a predisposition to developing or resisting breast cancer spread can be identified on an individual basis. Moffitt researchers will strive to evaluate inherited changes in DNA that are predictive in this instance. The team will evaluate SNPs in patients being treated for breast cancer. The research team includes Johnathan Lancaster, Ya-Tu Tsai and Thomas Sellers who collaborated with laboratories at the National Cancer Institute (Washington, DC, USA).
“We hope to identify biologic markers of metastasis to help classify those facing a higher metastasis risk,” Lee said. She continues: “We also aim to improve therapeutic decision-making and ability to better predict outcomes after a breast cancer diagnosis.” The researchers‘ ultimate goal is to “develop a cheek swab test for patients diagnosed with breast cancer to be able to quickly guide treatment decisions based on their inherited predisposition to develop advanced disease.”
– Written by Hardaman Baryan
Source: Moffitt researcher awarded GE grant to develop tool to detect breast cancer metastasis genetic risks: www.eurekalert.org/pub_releases/2012-04/hlmc-mra042712.php
Research reveals novel genes mutated in stomach cancer
A team of researchers from the Duke–National University of Singapore Graduate Medical School (Singapore) and the National Cancer Centre of Singapore (Singapore) have used state-of-the-art DNA sequencing technology to study the genetic variability of gastric cancers. By sequencing the exomes of approximately 18,000 genes in 15 different gastric cancers and their matched normal DNA, the scientists identified several frequently mutated genes. In total, the team found over 600 genes that were previously unknown to be mutated in stomach cancer. Their findings were published in early April in Nature Genetics.
In their study, the researchers found that the genes TP53, PIK3CA and ARID1A were all frequently mutated. They also observed mutations in the FAT4 gene and FAT4 deletions in 4% of gastric tumors. Of the genes identified in the study, the team noted that two of them, FAT4 and ARID1A, were of particular interest. FAT4 was identified in 5% of gastric cancers, while ARID1A was detected in 8% of gastric cancers. In functional assays, the researchers observed that both FAT4 and ARID1A exhibited tumor-suppressor activity. They concluded that somatic inactivation of these genes may be critical to the development of some gastric cancers.
Worldwide, stomach cancer is the second leading cause of cancer death. Owing to its often late detection and the relatively poor knowledge of its causes, treatment of stomach cancer is difficult and the prognosis is poor. The scientists hope that this research could lead to more effective treatment of gastric cancers and they are currently working on translating the work in this study into clinical applications.
– Written by Hannah Stanwix
Source: Zang ZJ, Cutcutache I, Poon SL et al. Exome sequencing of gastric adenocarcinoma identifies recurrent somatic mutations in cell adhesion and chromatin remodeling genes. Nat. Genet. 44, 570–574 (2012).