Variant Synonymizer: Platform to identify mutations defined in different ways is available now!
Over 2,000 gene–disease validation summaries are now available—no login required!
DIAPH2, encoded by HGNC:2877, is implicated in cytoskeletal regulation and cellular motility. Recent studies in laryngeal squamous cell carcinoma (MONDO_0005595) have focused on its role in tumor progression and metastasis.
In one multicenter study, a hemizygous deletion was identified as c.3116_3240del125 (p.Pro1039ArgfsTer42) in LSCC cell lines derived from lymph node metastases (PMID:30793164). Furthermore, analysis of 95 LSCC tumors revealed an enrichment of heterozygous single nucleotide variants affecting conserved domains exclusively in metastasizing cases (PMID:30793164), supporting the gene’s involvement in disease aggressiveness.
A second independent study assessed DIAPH2 polymorphisms in 230 male LSCC patients and demonstrated a significant association between specific alleles and advanced tumor stage (PMID:38844723). This genetic evidence, derived from distinct cohorts and methodologies, places the gene-disease association in the moderate range.
Functional studies outside the LSCC context have shown that DIAPH2 plays a role in actin elongation and microtubule stabilization, which are key to regulating cell movement (PMID:36689403). However, direct functional validation in LSCC models is limited, and the pathogenic mechanism in the context of laryngeal cancer remains to be fully elucidated.
Collectively, the genetic findings—comprising the recurrent deletion and single nucleotide variants—and the supportive, though indirect, functional data provide moderate evidence for the contribution of DIAPH2 alterations to the metastatic potential of laryngeal squamous cell carcinoma. Additional research may further solidify these observations and enhance their clinical utility in diagnostic and therapeutic decision-making.
Key take‑home message: DIAPH2 alterations represent a promising genetic marker for identifying aggressive, metastasizing laryngeal squamous cell carcinoma.
Gene–Disease AssociationModerateA hemizygous deletion (c.3116_3240del125) in LSCC cell lines from 95 tumors (PMID:30793164) and a significant association of DIAPH2 polymorphisms in 230 male LSCC patients (PMID:38844723) provide moderate evidence for this association. Genetic EvidenceModerateRecurrent deletions and single nucleotide variants observed in independent cohorts support a genetic association with LSCC metastasis. Functional EvidenceLimitedAlthough DIAPH2 functions in actin dynamics and cellular motility are well established in other contexts (PMID:36689403), direct functional evidence in LSCC remains limited. |