PRIZES. Tuesday May 17, Sahlgrenska Academy recognized seven dissertations that were defended at the faculty last year. Anna Rohlin, who received her PhD in clinical genetics, wrote the dissertation crowned the best dissertation of the year 2015.
“There are many dissertations from the Sahlgrenska Academy every year, and it feels fantastic to be recognized like this,” said Anna Rohlin.
Anna did her dissertation work in Margareta Nordling’s research group in the Department of Medical and Clinical Genetics. The group works in close collaboration with the clinic.
Cancer of the colon and rectum (colorectal cancer) is relatively common, with approximately 6000 new cases in Sweden each year. Approximately one in three cases depend to varying degrees on hereditary factors. There are several known genes where mutations cause an increased risk of cancer of the intestine, but there are still families for whom we do not know the exact genetic mutation that causes the family disease.
The family gathered on the mountain
Family reunions are unusual at Medicinareberget, but in the spring of 2014, Anna Rohlin’s research led to one in Birgit Thilander room. Around thirty members of the same family came together – there were family members from all over the country and even some who lived abroad – to obtain long-awaited information.
It was clear that this was a hereditary cause, since family members for generations suffered from colon cancer, among other things. Despite research efforts for more than 25 years, the genetic cause could not be found.
“We managed to identify the mutation, which is found in a gene that is important for the synthesis and repair of DNA in the cells. The defect affects the entire repair system, which can cause tumors not only in the intestines, but also in, for example, brain, pancreas and the uterus,” said Anna, who was one of the researchers at the Sahlgrenska Academy who gave a talk of the newfound genetic cause for the family reunion at Medicinareberget.
Opportunities to get tested
The discovery made it possible for the relatives to be able to choose to test themselves to see if they carried mutation.
“For the family, it meant a lot to know specifically which mutation they have in the family. Now they can, if they wish, find out whether or not they carry the mutation by seeking care through the Cancer Genetic Counseling at our clinic. Those who have the mutation are provided with a screening program to detect tumors at an earlier stage,” said Anna.
New discoveries
The gene where the mutation was present in the first family is called the POLE. On behalf of another family, Anna was able to identify a mutation in the gene GREM1 that caused their hereditary elevated risk for colorectal cancer. Discoveries of specific mutations are not only important for the families – they also add important knowledge to the broader research on tumor development and understanding of how tumors can be treated.
Mutations can also be found in regions outside the genes, for example, in the regions that control how genes are regulated. Mutations in the APC gene cause familial adenomatous polyposis, giving rise to hundreds or thousands of colorectal polyps [.] When it comes to classic familial adenomatous polyposis (FAP), the APC gene is almost always mutated. In cooperation with the Swedish Polyposis Registry at Karolinska Hospital, Anna Rohlin’s group was able to show that a mutation in a hitherto relatively unknown part of the APC gene regulatory region was mutated in a large FAP family with 150 family members. In addition to providing an explanation of the family’s illness, the discovery also led to completely new knowledge about how the APC gene works – one gene playing an important role in the tumor process in many different types of cancer.
Revolutionary method
The method she used arrived in the early 2000s, and it is referred to as Next Generation Sequencing (NGS) or massive parallel sequencing (MPS). It is a sequencing method used for parallel analysis of the whole genome or parts of genome. Next Generation Sequencing is now routine and part of the everyday work at Clinical Genetics.
“In the beginning it was a technically difficult and time-consuming method, because we had to set up all by ourselves. Today, there are many more complete software programs that we can use, and it’s faster to get started with the analyses,” said Anna, who herself also contributed to the gene panels that are now used throughout the world to more quickly identify mutations in patients with colorectal cancer.
Doctorate at half speed
Anna Rohlin had been working on her dissertation half-time, while she continued working with patient analyses in Clinical Genetics. Combining graduate studies of clinical work has only been an advantage, she thinks.
“The routes from discover to implementation in our clinical analyses are getting shorter and it’s very rewarding to see the results used immediately. It has been an advantage to be able to follow the technological developments over a longer period of time, because it is new technologies that made these discoveries possible.”
Anna defended her dissertation in January of last year, and is now working as a hospital geneticist in training at Clinical Genetics within the activities of Clinical Pathology and Genetics (CPG) at Sahlgrenska University Hospital. She combines her clinical work with a part-time position as a post-doc in Lund, where she is studying breast cancer families with whole genome sequencing.
“Genetic research is progressing rapidly, and we are increasingly shifting to personalized care, in which the treatment is based on genetic analyses of each individual patient,” said Anna, and she continued:
“I would like to continue to contribute to research with this focus, in line with the goals of the Swedish Cancer Society. It is the Swedish Cancer Society that funded my doctoral training and also accounts for most of the group’s research resources.”
You can read Anna Rohlin’s dissertation Hereditory Colorectal Cancer: Identification, Characterization and Classification of Mutations here: https://gupea.ub.gu.se/handle/2077/37108
A total of seven prize winners
The prize “Best dissertation at Sahlgrenska Academy” has been awarded since 2009 and is funded by a donation from Dr. Amt Vestby’s Research Foundation. Each year a total of seven prizes are awarded for dissertations defended during the past year. Other than the prize for the best dissertation at Sahlgrenska Academy, one dissertation from each Institute is also praised for its high quality.
The Institutes awarding prizes are:
Institute of Biomedicine
Nancy P. Nenonen – Norovirus Tracing in Environmental and Outbreak Settings – Experiences of waterborne, foodborne and nosocomial transmission
https://gupea.ub.gu.se/handle/2077/38460
Institute of Clinical Sciences
Per Wekell – Pediatric Autoinflammatory Diseases: Conceptual, Clinical, and Mechanistic Dimensions
https://gupea.ub.gu.se/handle/2077/39535
Institute of Medicine
Anna Darelid – Bone density, bone geometry and bone development in young men – the importance of pubertal timing and fracture history
https://gupea.ub.gu.se/handle/2077/38010
Institute of Neuroscience and Physiology
Ali Komai – Molecular and physiological regulation of adiponectin exocytosis in white adipocytes
https://gupea.ub.gu.se/handle/2077/39573
Institute of Odontology
Keisuke Nakamura – Mechanical and Microstructural Properties of Monolithic Zirconia
https://gupea.ub.gu.se/handle/2077/38002
Institute of Health and Care Sciences
Ulrika Bengtsson – Self-management in hypertension care
https://gupea.ub.gu.se/handle/2077/39563
