journal publication
Nearly all FLC tumors carry the fusion gene DNAJB1-PRKACA and the expressed protein chimera DNAJ-PKAc which is believed to be the driver of FLC formation. However, to identify potential new therapies for FLC, it is important to understand the specific mechanisms that drive the progression of the disease. In a previous study, the Sethupathy lab …
This study sequenced the DNA from FLC tumors and compared the results to the DNA from non-cancerous tissue from the same patients to identify the specific mutations that had occurred in the cancer. In the 10 samples examined, the only consistent mutation was the DNAJB1-PRKACA fusion gene. Since the only consistent mutation found was the …
The second Fibrolamellar Cancer Foundation Scientific Summit was held in Stamford, CT, USA, in November 2017. The goals of this meeting were to gather a diverse set of investigators, stimulate new collaborations, and devise new ways to inspire additional interest in the field. This meeting summary outlines the work supported by the Foundation and presented …
This publication retrospectively analyzes the clinicopathological factors and treatments affecting overall survival in FLC. Using the National Cancer Database, it identified 496 patients diagnosed with FLC between 2004 and 2015. Of those patients, resection was performed on 254 (51.2%), liver-directed therapy on 13 (2.6%), and liver transplantation on 15 (3.0%) patients. Median overall survival times …
This publication summarizes the current understanding of fibrolamellar carcinoma based on a review of currently available literature. It outlines the epidemiology, pathology, and biology of FLC, plus provides a high-level overview of the evidence supporting existing therapies for the disease — including surgical, radiotherapy, interventional radiology and systemic treatments. The full article can be read …
This recent publication describes six new PDX lines derived by direct implantation of tumor specimens, both from the liver (one primary and one recurrent tumor) and metastases. These facilitated the first reported large-scale screening of compounds for the ability to kill dissociated FLC tumor cells in short-term culture (72 hours). Active compounds were also assessed …
This article, published in Nature Reviews Gastroenterology & Hepatology, summarizes the key advances made in understanding the disease since the 2014 discovery that nearly all FLC tumors contain the DNAJB1-PRKACA chimeric fusion transcript. The paper outlines the advances made in understanding the molecular pathways driven by the fusion protein and the potential to identify actionable …
This study was the first published research effort that identified the DNAJB1-PRKACA chimeric transcript in fibrolamellar carcinoma tumors. By performing RNA sequencing on tumor and healthy tissue samples, a chimeric transcript was discovered that had not been previously reported in the literature. This fusion transcript arises due to a ~400-kilobase deletion on chromosome 19. In …
While the significance of the DNAJB1-PRKACA fusion gene in fibrolamellar carcinoma has been established and validated, the role of microRNAs (miRNAs) in FLC remains unclear. MicroRNAs have been implicated as drivers in many diseases including a variety of cancers. This study analyzed small RNA sequencing data to identify dysregulated miRNAs in FLC tumors and identified …