Researchers at the Center for Personalized Medicine at Children’s Hospital Los Angeles have made significant strides in uncovering new potential causes of a rare and lethal bone cancer known as chordoma. This aggressive bone tumor, occurring in approximately one in a million people in the U.S. each year, presents unique challenges, particularly in children where the tumors are predominantly found at the base of the skull.
The team, led by Xiaowu Gai, Ph.D. and Jaclyn Biegel, Ph.D., FACMG, recently published a groundbreaking genomic study in the journal Molecular Cancer Research. Through their research, they identified two classes of genetic causes for chordoma in children, shedding light on the underlying biology of this rare cancer.
Dr. Katrina O’Halloran, a pediatric neuro-oncologist and the first author of the study, emphasized the importance of understanding the distinct subtypes of chordoma in children to develop more effective treatment strategies. Unlike adult tumors, pediatric solid tumors are often driven by germline changes that increase the risk of cancer.
Past studies have revealed that one subtype of chordoma, poorly differentiated pediatric chordoma, is characterized by the loss of the SMARCB1 gene. This gene plays a crucial role in chromatin remodeling, a process that regulates how DNA is packaged within cells. While additional genetic risk factors and mutations have been identified in other subtypes of chordoma, a common biological mechanism connecting these variants was previously unknown.
Notably, the research team at CHLA expanded their investigation beyond the nuclear DNA genome to include mitochondrial DNA variants. Their dual-genome approach involved sequencing the coding regions of all genes in the nuclear DNA genome, as well as the entire mitochondrial DNA genome.
By exploring both nuclear and mitochondrial DNA, the researchers aimed to uncover comprehensive insights into the genetic underpinnings of chordoma in children. This holistic approach could pave the way for the development of more targeted and personalized treatment options for pediatric patients facing this rare and aggressive bone cancer.
