number of implantation sites bearing tumors was recorded. Short tandem repeat analysis was used to confirm that all origin of resulting tissues. Results: Seven of the 10 patient samples produced tumors in NSG mice. One tumor grew only from the cryopreserved specimen and one only from fresh specimen. STR analysis confirmed that all tissues matched the donor patient. Pathologic review of H&E stained slides demonstrated strong correlation in multiple histologic features between approaches. Conclusion: Immediate cryopreservation and later implantation produced viable PDX tissue at a rate that was not different from implantation of fresh tissue. This would permit investigators to perform key molecular analysis before investing time and resources in establishing PDXs that do not represent their scientific question. We believe this approach is a cost- and labor-efficient approach to establishing PDXs for correlative and trans- lational science. Author Disclosure: L. Abel: None. R. Hu: None. J.Y. Bruce: None. K.P. Nickel: None. R.J. Kimple: Employee; University of Wisconsin. Research Grant; Peloton Therapeutics, American Cancer Society, National Institute of Health, V Foundation for Cancer Research. Advisory Board; Galera therapeutics; PLOS One, International Journal of Radiation Oncology Biolog, Diabetes. 327 LSD1 Inhibitor and Cisplatin Combination Treatment of Sinonasal Squamous Cell Carcinoma Cell Lines L. Weatherford, 1 D. Kuhnell, 1 S. Palackdharry, 1 R. Vachon, 1 V. Takiar, 2 S. Langevin, 1 and T. Wise-Draper 3 ; 1 University of Cincinnati, Cincinnati, OH, 2 University of Cincinnati Department of Radiation Oncology, Cincinnati, OH, 3 University of Cincinnati Division of Hematology Oncology, Cincinnati, OH Purpose/Objective(s): Sinonasal squamous cell carcinoma (SNSCC) is relatively rare, accounting for less than 3% of all head and neck cancers. Despite intensive treatment, SNSCC is aggressive, with only approxi- mately 50% of patients surviving beyond five years after diagnosis. Treatment typically involves a combination of surgery and radiation with or without cytotoxic chemotherapy, such as cisplatin. Little is known about genetic mutations that occur in SNSCC, and even less is known about potential driving mutations. Next-generation whole-exome sequencing on SNSCC tumor samples and adjacent normal tissue revealed that eight out of ten tumors contained mutations in the lysine methyltransferase gene KMT2C, which has specificity for H3K4 methylation, a mark associated with transcriptionally active promoters. We hypothesized that somatic mutations in a H3K4 methyltransferase may result in loss or reduction of function, which would decrease H3K4 methylation, giving SNSCC cancer cells a proliferative advantage via silencing of tumor suppressor and DNA damage response and repair genes. We aimed to indirectly target these mutations in SNSCC cells through inhibition of KMT2C’s druggable demethylase counterpart, LSD1, which has specificity for demethylation of H3K4me1/2. Given the high prevalence of KMT2C mutations observed in SNSCC tumors, we hypothesized that inhibition of LSD1 would prevent loss of H3K4 methylation and deactivation of key tumor suppressor genes in SNSCC and thus synergize with the cytotoxic drug cisplatin due to increased response to DNA damage. Materials/Methods: Six SNSCC cell lines (SCCNC1, SCCNC4, SCCNC5, SCCNC6, SCCNC7, and UMSCC33) were treated with the indicated doses of cisplatin (Tocris) and the LSD1 inhibitor GSK2879552 (GlaxoSmithKline) alone or in combination. Proliferation was determined using the CellTiter 96Ò Aqueous One Solution Cell Proliferation Assay kit (Promega). Results: LSD1 inhibitor treatment alone did not result in decreased cellular proliferation. As expected, we observed varying sensitivity of the different cell lines to cisplatin alone. LSD1 inhibitor in combination with cisplatin resulted in an enhanced decrease of proliferation for several cell lines compared to cisplatin or the LSD1 inhibitor alone. Conclusion: Inhibition of LSD1 sensitized several SNSCC cell lines to cisplatin. We are currently in the process of genotyping the SNSCC cell lines for mutations in H3K4 methyltransferase genes. If it is confirmed that a high proportion of SNSCC tumors harbor mutations in H3K4 methy- transferases, further testing of LSD1 inhibitors or inhibitors of other H3K4 demethylases in in vivo models would be warranted with future possible translation to clinical trials. Author Disclosure: L. Weatherford: Employee; UC Health. D. Kuhnell: None. S. Palackdharry: None. R. Vachon: None. V. Takiar: None. S. Langevin: None. T. Wise-Draper: Head and Neck Cancer Precision Oncology Alliance Leader; Caris Life Sciences. 328 Molecular Profile of Early Stage Laryngeal Squamous Cell Carcinoma with Radiotherapy Resistance E. Yilmaz, 1 T.M. Schroeder, 1 D.Y. Lee, 1 B.J. Liem, 1 M.H. Turquie, 1 M.A. Ozbun, 1 D.J. McCance, 2 M. Spafford, 3 A. Cowan, 3 and G.N. Gan 4 ; 1 University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, 2 Department of Pathology, University of New Mexico, Albuquerque, NM, 3 Department of Surgery, University of New Mexico, Albuquerque, NM, 4 Department of Radiation Oncology, University of Kansas, Kansas City, KS Purpose/Objective(s): Early stage laryngeal squamous cell carcinomas (LSCC) are treated with radiotherapy or surgery with the intent of larynx preservation. Despite high cure rates with radiotherapy, local failure can be seen in 15-20% of the cases. Therefore, identifying underlying molecular determinants associated with local failure following radiotherapy may allow identification of patients needing escalation in therapy. Here we reviewed next-generation DNA sequencing analysis of 3 patients with early stage LSCC with rapid progression following local recurrence, and then analyzed the TCGA database on early stage LSCC to confirm the relevance of our findings. Materials/Methods: Next-generation sequencing was performed in a CLIA-certified platform following local recurrence in 3 patients with T1-2 LSCC treated with definitive radiotherapy. Clinical characteristic of these patients were reviewed. Promising gene targets were validated using early stage LSCC in the TCGA and analyzed using the cBioPortal web page. Results: All three patients demonstrated a similar mutational profile: CDKN2A loss, low tumor mutational burden (TMB) and microsatellite stable status (MSS). Two patients had co-alteration with CCND1 ampli- fication. All three patients had rapid progression in the neck with no distant metastasis. Two of the patients had progression after platinum based chemotherapy and one of these patients also received immunotherapy without response. The third patient had a rapidly enlarging lesion requiring total laryngectomy and adjuvant chemoradiotherapy to the nodal basin. Analysis of the TCGA data for the early stage LSCC identified 14 patients with stage I-II LSCC. CDKN2A alteration with mutation or deletion was observed in 6 patients; however, CCND1 amplification was observed only in 2 patients. The radiotherapy data were limited, and CDKN2A and CCND1 co-alteration was found in just one patient; that patient did not receive radiotherapy. Overall survival was shorter in the patients with CDKN2A alteration (22 months vs. 60 months), although it was statisti- cally not significant due to the small number of the patients (pZ0.13). Conclusion: Mutational signature of CDKN2A loss, low TMB, and MSS with CCND1 amplification may be associated with radiation resistance in early stage LSCC. However, the role of the TMB and radiotherapy has yet to be established. CDKN2A alterations are associated with poor outcome in early stage LSCC. Large scale comprehensive genomic analysis may help to identify mutational signatures capable of predicting response to radiotherapy in early stage LSCC. Author Disclosure: E. Yilmaz: None. T.M. Schroeder: Chairman - non- compensated; UNM Radiation Control Committee. Board Member - non- compensated; NM Cancer Care Alliance. D.Y. Lee: None. B.J. Liem: None. M.H. Turquie: None. M.A. Ozbun: Research Grant; Janssen Pharma. D.J. McCance: None. M. Spafford: None. A. Cowan: None. G.N. Gan: None. Volume 106  Number 5  Supplement 2020 Poster Presentations 1189