A New York City high school senior, Elana Simon, has identified a genetic alteration that may drive the development of a rare liver tumor, fibrolamellar hepatocellular carcinoma, which usually occurs in teens and young adults.
Simon, 18, was diagnosed with the disease at age 12.
Working with a set of professionals from New York institutions, she identified a lone genetic alteration in 100% of the tumors tested in the study (15/15). Notably, the alteration was not detected in matched normal tissue samples from study patients.
The evidence “suggests that this genetic alteration contributes to tumor pathogenesis,” write the authors, led by Simon and co-first author Joshua Honeyman, MD, of the department of surgery of Memorial Sloan Kettering Cancer Center in New York City.
Their new finding, which was published in the February 28th issue of Science , is a ground-breaking discovery.
“Little is known of [fibrolamellar hepatocellular carcinoma’s] molecular pathogenesis,” the authors write.
Or as Simon said in a video posted online: “Until now no one understood what causes this.”
The newly described genetic alteration, known as DNAJB1-PRKACA chimeric transcript, has not been reported in the literature and is not found in the COSMIC (Catalogue of Somatic Mutations in Cancer) database.
The authors are hopeful that this newly found fusion gene “may represent a diagnostic marker” and a “therapeutic target” for fibrolamellar hepatocellular carcinoma. Currently, there are no molecular diagnostic tests for the disease.
“Now we actually have a potential diagnostic for this cancer, which is great because the key to surviving fibrolamellar is finding it early,” said Simon.
She speaks from experience. Her tumor was completely removed at MSKCC 6 years ago by a team led by Michael LaQuaglia, MD, also a coauthor of the study.
“I was very lucky…I have been fine ever since,” Simon said.
I was very lucky…I have been fine ever since.
Surgery is the mainstay of treatment for this liver tumor, which has a clinical phenotype distinct from conventional hepatocellular carcinoma. The tumors “do not respond well to chemotherapy,” the authors say.
Overall survival is 30%-45% at 5 years.
Simon explained that before undertaking the current study she was an intern at a New York City lab and worked on a genomic analysis of pancreatic cancer. So, she had already cut her teeth in genomics.
“I decided to sequence the genome of my own cancer,” she explained.
I decided to sequence the genome of my own cancer.
Simon has had the good fortune of being born into a scientific family. Her father, Sanford Simon, PhD, the senior author of the paper, is from the Laboratory of Cellular Biophysics at Rockefeller University in New York City.
The Simons and their team performed whole genome and transcriptome sequencing of paired tumor and adjacent normal liver samples. To determine whether there were tumor-specific fusion transcripts among the coding RNA, they used the FusionCatcher program on RNA data from the tumors, metastases, and recurrences of 11 patients. Four more patients’ tumors were tested later, for a total of 15 patients.
“We have found the same change in every patient tested, which strongly suggests that this could be the change that is driving this cancer,’ said the younger Simon in her video.
Simon, who attends The Dalton School in Manhattan, has also helped develop the Fibrolamellar Registry, a Web site for patients who can share their medical information with each other and interested researchers and clinicians, according to a profile in The New Yorker .
Clinicians, computer scientists, and the National Institutes of Health’s office of rare diseases have already agreed to join the project as collaborators.