922P - Genomic instability as a biomarker for advanced cancer of the head and neck

Background

Genomic instability is an hallmark of cancer that has been associated to immune evasion, cancer progression and multidrug resistance. MOSCATO (NCT) was a prospective clinical trial evaluating the clinical benefit of high-throughput genomic analyses in patients with advanced solid tumors. In this study we investigated a genomic instability score based on somatic copy number alterations as determined by Single Nucleotide Polymorphism (SNP) array as a biomarker for head and neck cancer patients.

Methods

Extracted DNA from fresh frozen tumor was analyzed using high-resolution Affymetrix Cytoscan® HD array whereas extracted DNA from FFPE samples was analyzed using the Affymetrix Oncoscan® CNV assay. The absolute copy-number (ACN) profile was generated by ASCAT v3.1 through EaCoN v0.3.6 (https://github.com/gustaveroussy/EaCoN, PMID 36669143) on R v4.1.1 and then the genomic instability score (GIS) was estimated as the sum of the segment length multiplied by the absolute difference between segment copy number and the ASCAT estimated sample ploidy. This sum is reported to the reference genome length. In parallel, somatic mutation were assessed with a NGS panel covering including at least 75 critical oncogenes and tumor suppressor genes.

Results

SNP array data were available for 58 patients out of the 111 with head and neck cancers. 38 were men, 34 had squamous histology (SCC), 13 cystadenocarcinoma (ACC) and 11 other types (adenocarcinoma, mucinous carcinoma). Patients with SCC had higher GIS (median 0.53 for SCC vs 0.05 for ACC and 0.40 for others). At genomic level, the presence of TP53 (p < 0.001) and ATM (p 0.056) were associated with higher GIS. This was confirmed also after adjusting for histology. Conversely, GIS score was not associated with age. Patients with SCC that were positive for HPV (n=11) had lower GIS respect to HPV negatives (n=14, 0.24 vs 0.85, p 0.05) Higher GIS score was associated with decreased OS after adjusting for histology (HR 1.87, 95% CI 1.31 - 2.65, p < 0.001).

Conclusions

Genomic instability score based on SNP array copy number alterations profile is associated with worse prognosis in patients with carcinoma of the head and neck. Higher GIS score is found in squamous cell carcinomas and is associated with mutations in genes involved in cell cycle control.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.