Investigation of somatic mutation profiles and tumor evolution of primary oropharyngeal cancer and sequential lymph node metastases using multiregional whole-exome sequencing.

Autor: Sim NS; Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, South Korea., Shin SJ; Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea., Park I; Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.; Center for Precision Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea., Yoon SO; Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea., Koh YW; Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, South Korea., Kim SH; Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, South Korea., Park YM; Department of Otorhinolaryngology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
Jazyk: angličtina
Zdroj: Molecular oncology [Mol Oncol] 2023 Jun; Vol. 17 (6), pp. 981-992. Date of Electronic Publication: 2023 Mar 08.
DOI: 10.1002/1878-0261.13407
Abstrakt: Lymph node (LN) metastasis is an important factor in determining the treatment and prognosis of oropharyngeal squamous cell carcinoma (OPSCC). Here, we compared the somatic mutational profiles and clonal evolution of primary and metastatic LNs using multiregion sequencing of human papilloma virus (HPV)-positive OPSCC and HPV-negative OPSCC. We performed high-depth whole-exome sequencing (200×) of 76 samples from 18 patients with OPSCC (10 HPV-positive and 8 HPV-negative), including 18 primary tumor samples, 40 metastatic LN samples, and 18 normal tissue samples. Among 40 metastatic LNs, 22 showed extranodal extension (ENE). Mutation profiles of HPV-positive OPSCC and HPV-negative OPSCC were similar to those reported previously. Somatic mutations in CDKN2A and TP53 were frequently detected in HPV-negative OPSCC. Somatic mutations in HPV-positive OPSCC samples showed APOBEC-related signatures. Somatic mutations from metastatic LNs showed a different pattern than the primary tumor. Somatic mutations acquired in the WNT pathway during metastasis showed a significant relationship with ENE. Clonal evolution analysis of primary and metastatic LNs showed that, in some cases, each metastatic LN originated from a different primary tumor sub-clone.
(© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
Databáze: MEDLINE
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