Abstract 511: Prognostic relevance of 3q amplification in squamous cell carcinoma of the lung

Abstract

Abstract Introduction: Amplification of 3q is the most common genetic alteration identified in squamous cell carcinoma of the lung (LUSC) with the most frequent amplified region being 3q26-3q28. It has been described in preinvasive and invasive LUSC and represents one of the most striking molecular differences between LUSC and adenocarcinoma. Many studies evaluated the prognostic value of 3q amplification; however, they either studied the entire region (~40 genes) or 1-2 genes of biological relevance (e.g SOX-2, p63). In this analysis, we aim to describe the prognostic relevance of 3q by focusing on a minimal common region (MCR) of amplification within 3q constituted of 25 genes. Additionally, we examined the association between MCR amplification and other genetic alterations commonly found in LUSC, such as CDKN2A deletion. Results: We conducted an analysis of 499 cases of LUSC from The Cancer Genome Atlas (TCGA). The majority identified as white (90.2%) and 9.8% as African American (AA) or Asians; 73.7% were males, 7 patients had stage IV disease. We found amplification of MCR (chr3:181,711,924-183,428,101) ~1.7MB within a large amplified region between (chr3:170,169,718-187,736,569) ~17.5MB on chr 3q. All 25 genes within MCR were found to be frequently amplified. Molecular data was available for 476 patients in CBioPortal, amplification of MCR was found in 221 (44.3%) cases whereas 255 (51%) cases had no amplification. Median disease specific survival of MCR-amplified cases was significantly longer than non-amplified cases (NR versus 9.25 years; 95% LowerCI: 5.24; log-rank p<0.05). Median progression-free interval for amplified cases was 8 years (95% LowerCI: 5.1) versus 4.9 years (95% LowerCI: 3.5) for non-amplified cases (Log-rank p<0.05). In multivariable analysis, MCR amplification was associated with significantly improved progression-free survival (HR for progression 0.67, CI 0.47-0.95, p=0.024) and disease specific survival (HR for death 0.59, CI 0.38-0.94, p=0.025). CDKN2A homozygous deletion, a common genetic alteration in lung cancer, was detected in 126 patients, 70 with MCR amplification and 56 with no amplification. CDKN2A deletion was associated with MCR amplification (Fisher’s exact test p=0.02121; OR: 1.64, 95% CI: 1.07-2.54). Conclusion: Amplification of the 25-gene MCR within 3q was present in 44% of this cohort mainly composed of Caucasian patients with early stage LUSC. It was also associated with lower risk of progression and better disease specific survival. This analysis is a strong indicator for the prognostic relevance of the 25-gene MCR within 3q. We are further evaluating its prognostic relevance in a racially diverse patient population with advanced LUSC. Citation Format: Fawzi Abu Rous, Rebecca Chacko, Shannon Carskadon, Shanker Kalyana-Sundaram, Pin Li, Sunny Singh, Laila Poisson, Shirish Gadgeel, Nallasivam Palanisamy. Prognostic relevance of 3q amplification in squamous cell carcinoma of the lung [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 511.