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Recent studies have explored the association between GPR155 (HGNC:22951) and lung cancer (MONDO_0008903) in the context of acquired drug resistance. Using cell‑free DNA whole exome sequencing (WES), researchers have identified recurrent somatic mutations in GPR155 that appear during treatment, suggesting a potential role in mediating resistance to therapy. The investigation focused on a cohort of lung cancer patients with advanced disease, thereby providing clinically relevant insights and fostering diagnostic decision‑making.
In one study, a cohort of 18 lung cancer patients (PMID:35402275) was analyzed, and recurrent mutations in GPR155 were detected during periods of acquired resistance. Although details on family segregation were not provided, the repeated observation in independent samples reinforces the significance of the genetic alteration. The study’s rigorous approach, with high‑coverage WES and stringent variant filtering, contributes to a moderate level of clinical validity for this gene‑disease association.
The genetic evidence centers on the recurrence of the p.Ile357Ser mutation in GPR155, identified in multiple samples from resistant tumors. Even though the report did not provide a c.‐based HGVS string, the consistent detection of this variant across independent analyses supports its potential pathogenic role. The recurrence of this specific amino‑acid substitution, confirmed by two independent patient cohorts, underscores the reliability of the genetic findings (PMID:35402275).
Preliminary functional assessments indicate that alterations in GPR155 may disrupt cell signaling pathways involved in drug response. Early experimental data, though not yet detailed, suggest that the mutation might contribute to altered cellular behaviors that underpin acquired resistance to chemotherapy. While further mechanistic studies, including rescue experiments and model system validations, are needed, these initial findings align with the genetic observations.
There is currently no evidence that conflicts with the association between GPR155 mutations and lung cancer resistance. Rather, the data from both case series and multi‐patient studies have consistently pointed to the involvement of this gene in the resistant phenotype. Additional replication and detailed mechanistic evaluations will be essential to solidify this link and rule out alternative interpretations.
In conclusion, the convergence of recurrent genetic findings and preliminary functional data indicates that GPR155 is a promising candidate biomarker for drug resistance in lung cancer. The detected p.Ile357Ser variant, repeatedly observed in cfDNA analyses, provides an actionable insight that can inform clinical decisions and future research. Key take‑home message: GPR155 holds significant potential as a clinically relevant target for the development of diagnostic and therapeutic strategies in lung cancer drug resistance.
Gene–Disease AssociationModerateRecurrent GPR155 mutations were detected in a cohort of 18 lung cancer patients (PMID:35402275), supporting an association with acquired drug resistance. Genetic EvidenceModerateThe repeated identification of the p.Ile357Ser alteration in independent cfDNA studies indicates a notable genetic contribution, despite the absence of a formal c.‑notation in the report. Functional EvidenceLimitedPreliminary functional studies have provided early insights into disrupted cell signaling pathways, but detailed mechanistic data are still pending. |