TY  - JOUR
T1  - Connecting Noncoding Cancer Variants to Effector Genes: A Scoping Review of Functional Perturbation Strategies, Regulatory Context, and Evidence Supporting Causal Gene Assignment
A1  - Mariana Silva
A1  - Rafael Duarte
A1  - Camila Rocha
A1  - Paulo Ricardo
A1  - Ana Santos
A1  - Lucas Ferreira
JF  - Journal of Biochemical Technology
JO  - J Biochem Technol
SN  - 0974-2328
Y1  - 2026
VL  - 17
IS  - 4
DO  - 10.51847/v2hFoOjdoQ
SP  - 23
EP  - 33
N2  - Noncoding cancer-associated variants are frequently located in regulatory regions whose biological consequences cannot be inferred reliably from genomic position or statistical association alone. Establishing an effector gene requires evidence that a candidate variant alters regulatory function in an appropriate cellular context and that this alteration can be connected to a specific gene or downstream phenotype. This scoping review mapped experimental and computational strategies used between 2017 and 2025 to resolve that problem, with particular emphasis on massively parallel reporter assays, CRISPR-based regulatory perturbation, endogenous nucleotide editing, chromatin-interaction mapping, single-cell perturbation profiling, and integrative multi-omic approaches. Forty-eight unique records entered screening, 39 proceeded to eligibility assessment, and 32 evidence units were included. The evidence landscape showed that individual technologies interrogate different parts of the causal chain. Reporter assays efficiently detect allele-dependent regulatory activity but usually detach variants from endogenous chromatin; chromatin maps nominate physically plausible targets without establishing regulatory necessity; CRISPR-based element perturbation tests endogenous regulatory dependency but may not resolve the causal nucleotide; and base or prime editing provides more direct allele-specific evidence while remaining dependent on cellular state and assay context. Across the mapped literature, confidence in effector-gene assignment increased when fine mapping, regulatory-element activity, endogenous perturbation, target-gene response, and tissue-relevant chromatin evidence converged. The review therefore supports a conditional, evidence-layered interpretation of noncoding cancer variants in which causal gene assignment is strongest when alternative linked variants, neighboring genes, cell states, and regulatory routes have been experimentally discriminated.
UR  - https://jbiochemtech.com/article/connecting-noncoding-cancer-variants-to-effector-genes-a-scoping-review-of-functional-perturbation-a02vur1ktldt4zf
ER  -