Patient-keyed aggregation of public cancer genomic data imports clonal hematopoiesis into solid-tumor mutation matrices
Year: 2026
Type: preprint
Abstract: Large-scale reuse of public cancer genomic data begins by pooling studies into one patient-by-gene matrix, keyed on the patient. Records held under one patient identifier need not come from the same kind of specimen: three clonal-hematopoiesis studies in cBioPortal deposit blood normals sharing patient identifiers with tumors deposited elsewhere, so a patient-keyed merge records a hematopoietic clone as a tumor mutation. We linked 1, 282, 483 coding calls in 140 genes from 483 studies to patients, classified each by specimen type, and rebuilt the matrix with and without blood-derived calls. Blood normals supply 1.7% of calls but concentrate: 52.8% of patients flagged DNMT3A -mutant, 21.3% of TET2 and 19.7% of CHEK2 have no tumor-derived call in that gene, against 0.4% for TP53 . Those calls carry a hematopoietic gene spectrum and, in TP53 , hematopoietic allele fractions. The artifact reaches 65 further cohorts, almost all solid-tumor studies, exceeding one patient in ten in fifteen of them, and tracks the share of patients with a paired blood normal, not the disease ( r = 0.994, 45 cancer types). Correction lowers the pan-cancer DNMT3A rate by 45% and moves survival estimates further than chance removal of the same patients would. Two filter lines applied before aggregation remove it.
Source: medRxiv
Institutions: Stanford Medicine, Stanford University
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7221555288