Genomic Characteristics of Leiomyosarcoma: An AACR Project GENIE Study
Henna Ali1, Cinthiya Chander1, Elijah Torbenson1
1Creighton University School of Medicine, Omaha, NE, U.S.A.
Background/Aim:
Leiomyosarcoma is a rare and aggressive malignant smooth muscle tumor with limited treatment options and poor outcomes. Large-scale molecular characterization is needed to better understand tumor biology and support precision oncology, as prior studies have been limited by small cohort sizes, single-institution data, and restricted gene panels. This study aimed to characterize clinicogenomic features of leiomyosarcoma using the AACR Project GENIE 19.0 public dataset.
Patients And Methods:
We analyzed 1,017 tumor samples from 957 patients, evaluating demographic patterns, somatic mutation frequencies, copy number alterations, and genomic co-occurrence and exclusivity across primary and metastatic disease sites.
Results:
Females comprised 65.7% of cases and White patients 61.4%. The most frequently altered genes were TP53 (50.3%), RB1 (17.9%), and ATRX (15.9%), followed by KMT2D, MED12, NOTCH1, ATM, PTEN, ROS1, FAT1, BRCA2, and NOTCH3. Recurrent copy number alterations included RB1 homozygous deletion (24.4%), MAP2K4 amplification (18.4%), and TP53 homozygous deletion (15.5%). Significant co-occurrence was observed among TP53, RB1, ATRX, and PTEN alterations (q<0.05). Most genomic alterations were driven by primary tumors, whereas metastatic samples showed enrichment of IGF2 and AXIN1 alterations.
Conclusion:
These findings highlight recurrent alterations in TP53, RB1, and ATRX and suggest potential roles for IGF2 and AXIN1 in leiomyosrcoma metastatic disease that warrant further investigation.
