Published October 30, 2019
“Phenotypic Distinctions Between Mosaic Forms of Tuberous Sclerosis Complex” was published in May in the journal Genetics in Medicine.
Tuberous sclerosis complex (TSC) is one of the most common genetic tumor syndromes, affecting approximately 1 in 6,000 people. These individuals may develop tumors in many different organs, including the skin, lungs, kidneys and brain.
Within the TSC population, a significant proportion has mosaic TSC, meaning that only a fraction of their cells carry the causative mutation, Treichel notes. Because of this, routine genetic testing is not sensitive enough to detect the low levels of the mutation in their blood.
“The goal of our study was to improve our ability of detecting mosaic TSC mutations through the utilization of advanced genetic sequencing and to define the range of clinical phenotypes displayed in those with mosaic TSC compared to those with germline TSC,” Treichel says.
The researchers utilized next-generation sequencing technology capable of detecting mutations at levels of less than 1 percent.
“We first analyzed skin tumor samples because they are more enriched with cells carrying the mutation and we were then able to detect the same mutation in the blood at much lower levels,” Treichel says. “Through this method, we were able to diagnose mosaic TSC and deepen our understanding of the prognosis of those affected with mosaic TSC.”
Treichel says the research found that those with mosaic TSC have less severe disease and a lower risk of disease transmission to offspring than those with germline TSC.
“Additionally, we identified two cutaneous patterns of mosaic TSC that correspond with overall disease severity,” she says. “These concepts not only apply to TSC, but also to potentially hundreds of other genetic conditions that manifest in mosaic forms, especially as next-generation sequencing technology becomes more readily available.”
The paper was the result of Treichel‘s research conducted while taking part in the Medical Research Scholars Program (MRSP) at the NIH and Doris Duke Charitable Foundation Clinical (DDCF) Research Mentorship program, and was a continuation of the work initiated by Neera Nathan, MD, who was a DDCF mentee in 2014.
Among co-authors on the paper are Treichel’s mentor in the MRSP, Joel Moss, MD, PhD, of the Pulmonary Branch of the National Heart, Lung and Blood Institute, and his collaborator, Thomas Darling, MD, PhD, chair of dermatology at the Uniformed Services University of the Health Sciences.
“This was a team effort that wouldn’t have been possible without the expertise of several people,” says Treichel, noting she was co-first author with Lana Hamieh, MD, of the Division of Pulmonary Medicine and of Genetics at Brigham and Women’s Hospital, Harvard Medical School, who works in the laboratory of David Kwiatkowski, MD, PhD.
“They were responsible for sequencing our patient samples to identify the mosaic mutations,” she says. ”Once the mutations were identified, my role was to synthesize the genetic findings with our extensive clinical data.”
“After many hours reviewing patient records, staring at endless rows of data in Excel and brainstorming how to present the results, it was surreal to see the article available online and not just on my computer.”
Treichel says during her time at the NIH she was inspired by the dedication demonstrated by its investigators, many of whom have dedicated decades of their lives to solving even just a single problem.
“The NIH provided an invaluable opportunity to collaborate with top research scientists across many different disciplines,” she says. “I have developed a diverse skill set through my collaboration with statisticians, geneticists and physician-scientists within and outside of the NIH.”
“I now have a deeper appreciation for the dedication and time it takes to be a successful researcher,” Treichel adds. “The two years I have spent immersed in the research will serve as a solid foundation for my future research endeavors, as I hope to have my own lab one day.”
Treichel is excited to be back in Buffalo to complete her final year of medical school.
“So much has changed since I left two years ago. It has been so exciting to return to a brand new medical school building with state-of-the-art research facilities and to meet the newly recruited faculty,” she says.
“I look forward to reconnecting with my mentors in Buffalo and hope to continue building new and lasting relationships within the Buffalo medical community.”
Treichel has recently applied for a residency in dermatology.
“I hope to match at a program that will continue to foster my passion for research,” she says.