ING1 – Head and Neck Squamous Cell Carcinoma

ING1 (Inhibitor of Growth 1) has been implicated as a candidate tumor suppressor in head and neck squamous cell carcinoma (HNSCC). In a multi-patient study of 34 informative HNSCC tumors, loss of heterozygosity at chromosome 13q33-34 encompassing ING1 was observed in 68% of cases (PMID:10866301). In the subset of 23 tumors with allelic loss, three somatic missense mutations (c.644G>C (p.Cys215Ser), c.575C>A (p.Ala192Asp), c.647A>G (p.Asn216Ser)) were detected within the PHD finger and nuclear localization motifs in 6 tumors, likely abrogating ING1’s tumor suppressor function (PMID:10866301).

Functional studies in other cellular models demonstrate that ING1 regulates p53-dependent transcription and apoptosis. p33(ING1b) directly binds AT-motifs to repress AFP and enhance p21 via p53 acetylation, supporting a chromatin-remodeling mechanism (PMID:14522900). In Ing1-null mouse embryonic fibroblasts, oncogenic Ras fails to induce senescence due to reduced p53 stability and heterochromatin formation, corroborating haploinsufficiency as a pathogenic mechanism (PMID:17693408).

While recurrent somatic ING1 alterations and concordant functional data support a tumor-suppressor role, evidence in HNSCC remains limited to a single cohort. Additional studies are needed to establish the diagnostic and prognostic utility of ING1 in head and neck cancer.

References

• Cancer research • 2000 • Genomic structure of the human ING1 gene and tumor-specific mutations detected in head and neck squamous cell carcinomas. PMID:10866301
• Cancer research • 2003 • ING1 represses transcription by direct DNA binding and through effects on p53. PMID:14522900
• The Journal of biological chemistry • 2007 • Ing1 mediates p53 accumulation and chromatin modification in response to oncogenic stress. PMID:17693408

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