Whole-genome sequencing of a malignant granular cell tumor with metabolic response to pazopanib
Year: 2015
Type: preprint
Study design: Case Report
Abstract: Granular cell tumors are an uncommon soft tissue neoplasm. Malignant granular cell tumors comprise <2% of all granular cell tumors, are associated with aggressive behavior and poor clinical outcome, and are poorly understood in terms of tumor etiology and systematic treatment. Because of its rarity, the genetic basis of malignant granular cell tumor remains unknown. We performed whole-genome sequencing of one malignant granular cell tumor with metabolic response to pazopanib. This tumor exhibited a very low mutation rate and an overall stable genome with local complex rearrangements. The mutation signature was dominated by C>T transitions, particularly when immediately preceded by a 5' G. A loss-of-function mutation was detected in a newly recognized tumor suppressor candidate, BRD7. No mutations were found in known targets of pazopanib. However, we identified a receptor tyrosine kinase pathway mutation in GFRA2 that warrants further evaluation. To the best of our knowledge, this is only the second reported case of a malignant granular cell tumor exhibiting a response to pazopanib, and the first whole-genome sequencing of this uncommon tumor type. The findings provide insight into the genetic basis of malignant granular cell tumors and identify potential targets for further investigation.
Source: Molecular Case Studies
DOI: 10.1101/mcs.a000380
Authors: Lei Wei, Song Liu, Jeffrey Conroy, Jianmin Wang, Antonios Papanicolau-Sengos, Sean T. Glenn, Mitsuko Murakami, Lu Liu, Qiang Hu, Jacob Conroy, Kiersten Marie Miles, David E. Nowak, Biao Liu, Maochun Qin, Wiam Bshara, Angela R. Omilian, Karen Head, Michael Bianchi, Blake Burgher, Christopher Darlak, John Kane, Mihai Merzianu, Richard Cheney, Andrew Fabiano, Kilian Salerno, Chetasi Talati, Nikhil I. Khushalani, Donald L. Trump, Candace S. Johnson, Carl D. Morrison
Institutions: Roswell Park Comprehensive Cancer Center, Inova Health System
Language: English
Topic: Tumors and Oncological Cases
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W2256781973