What type of study is this?

This is a Cohort Study study (also classified as: Experimental Study).

September 19, 2025

Abstract B098: Global-scale patient-partnered genomic databanking: unlocking therapeutic and biological insights in rare cancers through decentralized recruitment and open data sharing

Key Points

Decentralized genomic profiling enhances therapies for patients with rare cancers, accelerating discovery and equity in treatment.
Out of 333 patients, 86.8% underwent successful sequencing, revealing actionable MAPK alterations in histiocytosis cases.
The methodology employed targeted sequencing and whole exome recapture, integrating genomic findings with clinical metadata for real-time sharing.
Unlocking actionable biology in rare cancers may enable algorithm-driven treatment matching, particularly in underserved populations.

Abstract

Abstract Background: Rare cancers are critically under-characterized due to limited patient numbers, poor trial accrual, and restricted access to genomic testing, barriers that disproportionately affect patients in low- and middle-income countries (LMICs). The Make-an-IMPACT program offers a scalable, patient-partnered model that overcomes these challenges by leveraging digital recruitment, no-cost genomic profiling, and open-access data dissemination via cBioPortal. Methods: Patients with histiocytosis, ovarian germ cell tumors (GCTs), and other rare malignancies were enrolled globally via social media outreach, advocacy networks, and clinician referrals. Tumor and matched germline DNA underwent MSK-IMPACT targeted sequencing; a subset of ovarian GCTs was further analyzed via whole exome recapture. Genomic findings were integrated with clinical metadata, returned to patients and providers, and shared through the public Make-an-IMPACT cBioPortal study. Results: Of 333 patients enrolled across 17 countries, 250 (86. 8%) successfully underwent sequencing. In histiocytosis, recurrent MAPK pathway alterations were identified, including BRAF V600E, NRAS A59E79 in-frame deletions, and MAP2K1 mutations. Among those receiving genomically matched therapies (e. g. , vemurafenib, cobimetinib), 93% (13/14) derived clinical benefit. In the ovarian GCT cohort, whole exome sequencing identified a novel haploid genomic signature in a subset of tumors—confirmed by ABSOLUTE allelic copy number analysis. Additional findings included KRAS, TP53, KIT, PIK3CA, and NRAS mutations, with most inferred to be clonal. Although actionable mutations were present in only 28% of ovarian GCTs, two tumors exhibited high tumor mutational burden (TMB), including one case of complete response to pembrolizumab. Conclusions: Decentralized, patient-partnered genomic profiling paired with real-time data sharing accelerates rare cancer discovery and enhances equity in precision oncology. This approach removes infrastructure barriers, empowers providers globally, and uncovers targetable biology, including actionable MAPK alterations in histiocytosis and novel haploid states in ovarian GCTs. Future directions include algorithm-driven treatment matching and survivorship research in underserved populations. Citation Format: Seyram A. Doe-Tetteh, Sabrina Y. Camp, Jett Crowdis, Anne Marie Noronha, Tina Alano, Dalicia Reales, Agnes Viale, Mark Donoghue, Nicholas D. Socci, Michael F. Berger, Hikmat A. Al-Ahmadie, Samuel A. Funt, Darren R. Feldman, Eli L. Diamond, Eliezer Van Allen, David B. Solit. Global-scale patient-partnered genomic databanking: unlocking therapeutic and biological insights in rare cancers through decentralized recruitment and open data sharing abstract. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34 (9 Suppl): Abstract nr B098.

Mark Helpful

Bookmark

Relay