Federal Project Grant Award Summary

Baylor College of Medicine received a $321,000 Project Grant from the National Cancer Institute (NCI) under the Cancer Cause and Prevention Research program (CFDA 93.393) awarded June 1, 2026, with a completion date of May 31, 2028. This research initiative will characterize germline and somatic genetic variants contributing to Langerhans Cell Histiocytosis (LCH) pathogenesis, a rare inflammatory myeloid neoplasia affecting young children with significant treatment-resistant disease and neurodegeneration risks. The project will analyze large-scale genomic sequence data from pediatric cancer case-parent trios generated through the Gabriella Miller Kids First research program to define inherited genetic effects on LCH risk and adverse clinical outcomes, complementing prior genome-wide association study findings that identified the SMAD6 variant as a risk factor while addressing the approximately 20% of LCH tumors lacking identified driver somatic mutations.

The research will investigate the role of de novo mutations in LCH susceptibility by leveraging existing genomic datasets to clarify the "misguided myelomonocytic precursor model" of disease pathogenesis, with particular focus on understanding how germline genetic components interact with somatic mutations in MAPK pathway genes (including BRAFV600E) to determine disease extent, clinical outcomes, and neurodegeneration progression. Deliverables will include comprehensive genetic analysis results, characterization of germline variants associated with LCH risk stratification, and findings that may inform improved patient risk assessment and therapeutic approaches for this pediatric cancer population.