TY - JOUR
T1 - ROS1 Alterations as a Potential Driver of Gliomas in Infant, Pediatric, and Adult Patients
AU - Meredith, David M.
AU - Cooley, Linda D.
AU - Dubuc, Adrian
AU - Morrissette, Jennifer
AU - Sussman, Robyn T.
AU - Nasrallah, MacLean P.
AU - Rathbun, Pamela
AU - Yap, Kai Lee
AU - Wadhwani, Nitin
AU - Bao, Liming
AU - Wolff, Daynna J.
AU - Ida, Cristiane
AU - Sukhanova, Madina
AU - Horbinski, Craig
AU - Jennings, Lawrence J.
AU - Farooqi, Midhat
AU - Gener, Melissa
AU - Ginn, Kevin
AU - Kam, Kwok Ling
AU - Sasaki, Koji
AU - Kanagal-Shamanna, Rashmi
AU - Alexandrescu, Sanda
AU - Brat, Daniel
AU - Lu, Xinyan
N1 - Publisher Copyright:
© 2023
PY - 2023/11
Y1 - 2023/11
N2 - Gliomas harboring oncogenic ROS1 alterations are uncommon and primarily described in infants. Our goal was to characterize the clinicopathological features and molecular signatures of the full spectrum of ROS1 fusion–positive gliomas across all age groups. Through a retrospective multi-institutional collaboration, we report a collection of unpublished ROS1 fusion gliomas along with the characterization and meta-analysis of new and published cases. A cohort of 32 new and 58 published cases was divided into the following 3 age groups: 19 infants, 40 pediatric patients, and 31 adults with gliomas. Tumors in infants and adults showed uniformly high-grade morphology; however, tumors in pediatric patients exhibited diverse histologic features. The GOPC::ROS1 fusion was prevalent (61/79, 77%) across all age groups, and 10 other partner genes were identified. Adult tumors showed recurrent genomic alterations characteristic of IDH wild-type glioblastoma, including the +7/−10/CDKN2A deletion; amplification of CDK4, MDM2, and PDGFRA genes; and mutations involving TERTp, TP53, PIK3R1, PIK3CA, PTEN, and NF1 genes. Infant tumors showed few genomic alterations, whereas pediatric tumors showed moderate genomic complexity. The outcomes were significantly poorer in adult patients. Although not statistically significant, tumors in infant and pediatric patients with high-grade histology and in hemispheric locations appeared more aggressive than tumors with lower grade histology or those in nonhemispheric locations. In conclusion, this study is the largest to date to characterize the clinicopathological and molecular signatures of ROS1 fusion–positive gliomas from infant, pediatric, and adult patients. We conclude that ROS1 likely acts as a driver in infant and pediatric gliomas and as a driver or codriver in adult gliomas. Integrated comprehensive clinical testing might be helpful in identifying such patients for possible targeted therapy.
AB - Gliomas harboring oncogenic ROS1 alterations are uncommon and primarily described in infants. Our goal was to characterize the clinicopathological features and molecular signatures of the full spectrum of ROS1 fusion–positive gliomas across all age groups. Through a retrospective multi-institutional collaboration, we report a collection of unpublished ROS1 fusion gliomas along with the characterization and meta-analysis of new and published cases. A cohort of 32 new and 58 published cases was divided into the following 3 age groups: 19 infants, 40 pediatric patients, and 31 adults with gliomas. Tumors in infants and adults showed uniformly high-grade morphology; however, tumors in pediatric patients exhibited diverse histologic features. The GOPC::ROS1 fusion was prevalent (61/79, 77%) across all age groups, and 10 other partner genes were identified. Adult tumors showed recurrent genomic alterations characteristic of IDH wild-type glioblastoma, including the +7/−10/CDKN2A deletion; amplification of CDK4, MDM2, and PDGFRA genes; and mutations involving TERTp, TP53, PIK3R1, PIK3CA, PTEN, and NF1 genes. Infant tumors showed few genomic alterations, whereas pediatric tumors showed moderate genomic complexity. The outcomes were significantly poorer in adult patients. Although not statistically significant, tumors in infant and pediatric patients with high-grade histology and in hemispheric locations appeared more aggressive than tumors with lower grade histology or those in nonhemispheric locations. In conclusion, this study is the largest to date to characterize the clinicopathological and molecular signatures of ROS1 fusion–positive gliomas from infant, pediatric, and adult patients. We conclude that ROS1 likely acts as a driver in infant and pediatric gliomas and as a driver or codriver in adult gliomas. Integrated comprehensive clinical testing might be helpful in identifying such patients for possible targeted therapy.
KW - GOPC::ROS1
KW - ROS1 fusion–positive glioma
KW - adult-type
KW - copy number alterations (CNAs)
KW - infant-type hemispheric glioma
KW - pediatric-type
UR - http://www.scopus.com/inward/record.url?scp=85178499328&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85178499328&partnerID=8YFLogxK
U2 - 10.1016/j.modpat.2023.100294
DO - 10.1016/j.modpat.2023.100294
M3 - Article
C2 - 37532182
AN - SCOPUS:85178499328
SN - 0893-3952
VL - 36
JO - Modern Pathology
JF - Modern Pathology
IS - 11
M1 - 100294
ER -