Henrike Reder1, Steffen Wagner2, Ulrike Gamerdinger3, Sarah Sandmann4, Nora Wuerdemann5, Andreas Braeuninger3, Martin Dugas4, Stefan Gattenloehner3, Jens Peter Klussmann5, Claus Wittekindt2. 1. Department of Otorhinolaryngology, Head and Neck Surgery, Justus-Liebig University Giessen, 35392 Giessen, Germany. Electronic address: henrike.reder@hno.med.uni-giessen.de. 2. Department of Otorhinolaryngology, Head and Neck Surgery, Justus-Liebig University Giessen, 35392 Giessen, Germany. 3. Department of Pathology, Justus-Liebig University Giessen, 35392 Giessen, Germany. 4. Institute of Medical Informatics, Westphalian Wilhelms University Muenster, 48149 Muenster, Germany. 5. Department of Otorhinolaryngology, Head and Neck Surgery, Justus-Liebig University Giessen, 35392 Giessen, Germany; Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty, University Hospital Cologne, 50931 Cologne, Germany.
Abstract
OBJECTIVES: Despite improved survival rates of patients with HPV-associated OPSCC, a subset has distant metastasis or develops local recurrence during follow-up. To investigate potential underlying genetic alterations, we analyzed patients with HPV-driven OPSCC who suffered from recurrence in comparison to matching pairs with successful tumor control. MATERIALS AND METHODS: We performed chromosomal copy number analyses and targeted next generation sequencing using a custom panel comprising genes that are frequently mutated in HPV-associated OPSCC. RESULTS: Specific differences regarding chromosomal aberrations were not observed between both groups. In HPV-driven OPSCC from patients with recurrence we found higher mutation rates compared to patients with successful tumor control. Especially mutation rates of HRAS (p ≤ 0.05) PIK3R1, STK11 and TP63 (p ≤ 0.1 each) were statistically significant or trending towards significance. The respective genes can be linked to transcription factors and signaling pathways involved in cell cycle regulation, proliferation and survival. Additionally, combinations of alterations were observed on chromosomes 16 and 19, which might also influence outcome. CONCLUSION: Patients with HPV-driven OPSCC who develop recurrence or have metastasis may be defined by genetic alterations that might be responsible for poor outcome after standard therapy. This might be of importance for stratification in future de-escalation and targeted therapy.
OBJECTIVES: Despite improved survival rates of patients with HPV-associated OPSCC, a subset has distant metastasis or develops local recurrence during follow-up. To investigate potential underlying genetic alterations, we analyzed patients with HPV-driven OPSCC who suffered from recurrence in comparison to matching pairs with successful tumor control. MATERIALS AND METHODS: We performed chromosomal copy number analyses and targeted next generation sequencing using a custom panel comprising genes that are frequently mutated in HPV-associated OPSCC. RESULTS: Specific differences regarding chromosomal aberrations were not observed between both groups. In HPV-driven OPSCC from patients with recurrence we found higher mutation rates compared to patients with successful tumor control. Especially mutation rates of HRAS (p ≤ 0.05) PIK3R1, STK11 and TP63 (p ≤ 0.1 each) were statistically significant or trending towards significance. The respective genes can be linked to transcription factors and signaling pathways involved in cell cycle regulation, proliferation and survival. Additionally, combinations of alterations were observed on chromosomes 16 and 19, which might also influence outcome. CONCLUSION:Patients with HPV-driven OPSCC who develop recurrence or have metastasis may be defined by genetic alterations that might be responsible for poor outcome after standard therapy. This might be of importance for stratification in future de-escalation and targeted therapy.
Authors: Ryan M Murphy; Jason Tasoulas; Alessandro Porrello; Miranda B Carper; Yi-Hsuan Tsai; Alisha R Coffey; Sunil Kumar; Peter Yf Zeng; Travis P Schrank; Bentley R Midkiff; Stephanie Cohen; Ashley H Salazar; Michele C Hayward; D Neil Hayes; Andrew Olshan; Gaorav P Gupta; Anthony C Nichols; Wendell G Yarbrough; Chad V Pecot; Antonio L Amelio Journal: Cancer Res Commun Date: 2022-09-15
Authors: Henrike Reder; Steffen Wagner; Nora Wuerdemann; Christine Langer; Sarah Sandmann; Andreas Braeuninger; Martin Dugas; Stefan Gattenloehner; Claus Wittekindt; Jens Peter Klussmann Journal: Cancer Med Date: 2021-02-01 Impact factor: 4.452