145P - Unveiling the molecular landscape of head and neck cancer: Pathway dysregulations and potential therapeutic targets

Background

Head and neck cancers (HNCs) comprise a diverse set of malignancies driven by complex molecular mechanisms, often resulting in poor clinical outcomes. Identifying the molecular pathways involved in HNC can aid in the development of personalized treatments.

Methods

We performed a comprehensive molecular analysis on 220 HNC samples, examining gene expression for 20,802 genes with targeted transcriptome analysis in 106 cases. Additionally, PD-L1 IHC, MSI, and TMB profiling were conducted on a subset of samples.

Results

Targeted transcriptome analysis confirmed dysregulation in pathways pertained to Cell cycle regulation, Apoptosis, DNA damage response and Transcriptional regulation with DLGAP5, CASP14, BCL2, and JUN as the most dysregulated genes. Genome wide copy number analysis in 74 cases revealed chromosome arm losses in 34% and gain in 9%. 4p, 19p, 1p were the commonly involved regions among others. Mutations were predominantly observed in tumor suppressor genes (68%), compared to oncogenes (32%). Frequent mutations were seen in genes such as TP53 (67%), CDKN2A(20%), PIK3CA (14%), TERT (15%) and NOTCH1(5%). HRAS mutations were seen in 5% and EGFR in 1%. Amplifications were observed in EGFR (6%), MYC (12%), FGF4 (10%) and CCND1(8%). Fusion was rare event with novel and recurrent fusion events observed involving genes like FGFR3 and BRAF. High TMB (≥10 muts/mb) was seen in 17% (Median 6, range 0 to 28). None of the tumors showed MSI-high status (n=63). Positivity of PD-L1 was the most frequent ICI indicator, with PD-L1 22-C3 CPS ≥1 in 66% (50 of 76). PD-L1 28-8 analysis revealed TPS ≥1 in 46% % (36 of 78). Higher PD-L1 positivity was observed in TMB high samples (76% vs 59%). Table: 145P

Prevalence of ESCAT tier wise alterations

Conclusions

This study underscores the genetic heterogeneity of HNCs. It reinforces the limited availability of targetable alterations, while highlighting unique pathways that could be potential targets for future therapeutic developments.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Datar Cancer Genetics.

Funding

Has not received any funding.

Disclosure

N. Rohatgi, S. Limaye: Non-Financial Interests, Personal, Advisory Board: Datar Cancer Genetics. S. Schuster, S. Apurwa: Financial Interests, Personal, Full or part-time Employment: Datar Cancer Genetics. All other authors have declared no conflicts of interest.