Not targetable No mutation Level 1 ( n = 55, 35%) PIK3CA (n = 32, 20%) HRD genes (n = 20, 14%) Level 2 (n = 7, 4%) Level 3 (n = 3, 2%) Level 4 (n = 10, 6%) Table 1: Clinical and histopathological characteristics of the cohort. FPN 139P Genomic prognostic and potential theragnostic factors in anal squamous cell carcinoma treated with abdominoperineal resection Conclusion • In patients with HPV-positive ASCC treated by APR, PIK3CA exon 9/20 and KMT2C pathogenic variants are independent prognostic factors of overall survival. • The high prevalence of alterations with potential theragnostic value strongly supports the use of genomic profiling to allow patient enrollment in precision medicine clinical trials. A. Hamza1, J. Masliah-Planchon1, C. Neuzillet2, J. H. Lefèvre3, M. Svrcek4, S. Vacher1, C. Bourneix1, M. Delaye2, D. Goéré5, P. Dartigues6, E. Samalin7, M. Hilmi2, J. Lazartigues2, E. Girard8, J. Emile9, E. Rigault10, V. Dangles-Marie11,19, N. Rioux-Leclercq12, C. de la Fouchardiere13, D. Tougeron14, A. Casadei-Gardini15, P. Mariani16, F. Peschaud17, W. Cacheux18, A. Lièvre10,20, I. Bièche1,21 abderaouf.hamza@curie.fr 1: Genetics Department, Institut Curie, PSL Research University, Paris, France, 2: Medical Oncology Department, Institut Curie, PSL Research University, Saint-Cloud, France, 3: Sorbonne Université, Department of Digestive Surgery, Assistance Publique-Hôpitaux de Paris, Hôpital Saint Antoine, Paris, France, 4: Pathology Department, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, France, 5: Digestive Surgery Department, Gustave Roussy Institute, Villejuif, France, 6: Pathology Department, Gustave Roussy Institute, Villejuif, France, 7: Medical Oncology Department, Institut du Cancer de Montpellier, Montpellier, France, 8: INSERM U900 Research unit, Institut Curie, PSL Research University, Paris, France, 9: Université Paris-Saclay, Assistance Publique-Hôpitaux de Paris, UVSQ, BECCOH, Hôpital Ambroise-Paré, Pathology Department, Boulogne-Billancourt, France, 10: Gastroenterology Department, Rennes University Hospital, Rennes, France, 11: Laboratory of preclinical investigation, Translational Research Department, Institut Curie, PSL Research University, Paris, France, 12: Pathology Department, University Hospital of Rennes, Rennes, France, 13: Medical Oncology Department, Centre Léon Bérard, Lyon, France, 14: Department of Gastroenterology and Hepatology, Poitiers University Hospital, Poitiers, France, 15: Department of Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, Milan, Italy, 16: Department of Surgery, Institut Curie, PSL Research University, Paris, France, 17: Department of Digestive and Oncologic Surgery, Ambroise Paré Hospital, Versailles Saint-Quentin University, Paris Saclay University, Boulogne-Billancourt, France, 18: Medical Oncology Department, Hôpital Privé Pays de Savoie, Annemasse, France, 19: Faculty of Pharmaceutical and Biological Sciences, Paris Cité University, Paris, France, 20: Rennes 1 University; Inserm U1242, COSS (Chemistry Oncogenesis Stress Signaling), Rennes, France, 21: INSERM U1016, Faculty of Pharmaceutical and Biological Sciences, Paris Cité University, Paris, France Background • The management of anal squamous cell carcinoma (ASCC) has yet to benefit from the progress of precision medicine. • The few prognostic factors assessed to date are insufficient to accurately predict clinical outcomes. • Genomic analyses could identify new prognostic biomarkers and potential avenues for targeted therapies. HPV status Characteristic N Overall, N = 158 Positive, N = 1411 Negative, N = 171 p-value2 Age 158 57 (49, 66)1 58 (50, 66) 52 (49, 62) 0.43 Sexe 158 0.001 Female 102 (65%) 97 (69%) 5 (29%) Male 56 (35%) 44 (31%) 12 (71%) Stage 145 0.47 I 14 (10%) 11 (9%) 3 (20%) II 70 (48%) 63 (48%) 7 (47%) III 59 (41%) 54 (42%) 5 (33%) IV 2 (1%) 2 (2%) 0 (0%) ypT 156 0.15 ypT1 19 (12%) 19 (14%) 0 (0%) ypT2 60 (38%) 50 (36%) 10 (59%) ypT3 32 (2