1. Department of Oral Pathology, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials, Beijing, China; 2. Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions, Chinese Academy of Medical Sciences (2019RU034), Beijing, China; 3. Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China
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Received
Revised
Published
09 Aug 2023
02 Dec 2023
01 Jan 2024
Issue Date
10 Jul 2024
Abstract
Oral squamous cell carcinoma (OSCC) is the predominant type of oral cancer, while some patients may develop oral multiple primary cancers (MPCs) with unclear etiology. This study aimed to investigate the clinicopathological characteristics and genomic alterations of oral MPCs. Clinicopathological data from patients with oral single primary carcinoma (SPC, n = 202) and oral MPCs (n = 34) were collected and compared. Copy number alteration (CNA) analysis was conducted to identify chromosomal-instability differences among oral MPCs, recurrent OSCC cases, and OSCC patients with lymph node metastasis. Whole-exome sequencing was employed to identify potential unique gene mutations in oral MPCs patients. Additionally, CNA and phylogenetic tree analyses were used to gain preliminary insights into the molecular characteristics of different primary tumors within individual patients. Our findings revealed that, in contrast to oral SPC, females predominated the oral MPCs (70.59%), while smoking and alcohol use were not frequent in MPCs. Moreover, long-term survival outcomes were poorer in oral MPCs. From a CNA perspective, no significant differences were observed between oral MPCs patients and those with recurrence and lymph node metastasis. In addition to commonly mutated genes such as CASP8, TP53 and MUC16, in oral MPCs we also detected relatively rare mutations, such as HS3ST6 and RFPL4A. Furthermore, this study also demonstrated that most MPCs patients exhibited similarities in certain genomic regions within individuals, and distinct differences of the similarity degree were observed between synchronous and metachronous oral MPCs.
Xuan Zhou, Xinjia Cai, Fengyang Jing, Xuefen Li, Jianyun Zhang, Heyu Zhang, …Tiejun Li.
Genomic alterations in oral multiple primary cancers. International Journal of Oral Science, 2024, 16(0): 13 https://doi.org/10.1038/s41368-023-00265-w
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References
1. Liu, T.-Y.et al.Mutation analysis of second primary tumors in oral cancer in Taiwanese patients through next-generation sequencing.Diagnostics 12, 951(2022). 2. Zecha J. A.E. M. et al. Low-level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 2: proposed applications and treatment protocols.Support Care Cancer 24, 2793-2805 (2016). 3. Shield, K. D.et al.The global incidence of lip, oral cavity, and pharyngeal cancers by subsite in 2012.CA Cancer J. Clin. 67, 51-64 (2017). 4. Kyrgidis, A.et al.Clinical, histological and demographic predictors for recurrence and second primary tumours of head and neck basal cell carcinoma. A 1062 patient-cohort study from a tertiary cancer referral hospital.Eur. J. Dermatol. 20, 276-282 (2010). 5. Warren S & Gates O. Multiple primary malignant tumors. a survey of the literature and a statistical study. Am. [J]. Cancer. 16, 1358-1414 (1932). 6. International Association of Cancer Registries. International rules for multiple primary cancers.Asian Pac. J. Cancer Prev. 6, 104-106 (2005). 7. Thakur, M. K.et al.Risk of second lung cancer in patients with previously treated lung cancer: analysis of surveillance, epidemiology, and end results (SEER) data.J. Thorac. Oncol. 13, 46-53 (2018). 8. Shiga, K.et al.Distinct features of second primary malignancies in head and neck cancer patients in Japan.Tohoku J. Exp. Med. 225, 5-12 (2011). 9. Bugter, O.et al.Survival of patients with head and neck cancer with metachronous multiple primary tumors is surprisingly favorable.Head Neck 41, 1648-1655 (2019). 10. Baba, Y.et al.Clinical and prognostic features of patients with esophageal cancer and multiple primary cancers: a retrospective single-institution study.Ann. Surg. 267, 478-483 (2018). 11. Pandurengan, R. K.et al.Survival of patients with multiple primary malignancies: a study of 783 patients with gastrointestinal stromal tumor.Ann. Oncol. 21, 2107-2111 (2010). 12. Braakhuis B. J.M. et al. Second primary tumors and field cancerization in oral and oropharyngeal cancer: molecular techniques provide new insights and definitions.Head Neck 24, 198-206 (2002). 13. Detterbeck, F. C.et al.The IASLC Lung Cancer Staging Project: background data and proposed criteria to distinguish separate primary lung cancers from metastatic foci in patients with two lung tumors in the forthcoming eighth edition of the TNM classification for lung cancer.J. Thorac. Oncol. 11, 651-665 (2016). 14. Rettori, M. M.et al.TIMP3 and CCNA1 hypermethylation in HNSCC is associated with an increased incidence of second primary tumors.J. Transl. Med. 11, 316(2013). 15. Li, F.et al.p73 G4C14-to-A4T14 polymorphism and risk of second primary malignancy after index squamous cell carcinoma of head and neck. Int. J. Cancer 125, 2660-2665 (2009). 16. Lei, D.et al.FAS and FASLG genetic variants and risk for second primary malignancy in patients with squamous cell carcinoma of the head and neck. Cancer Epidemiol. Biomark. Prev. 19, 1484-1491 (2010). 17. Wang, Z.et al.Genetic variants of p27 and p21 as predictors for risk of second primary malignancy in patients with index squamous cell carcinoma of head and neck.Mol. Cancer 11, 17(2012). 18. Jin, L.et al.Genetic variants in p53-related genes confer susceptibility to second primary malignancy in patients with index squamous cell carcinoma of head and neck.Carcinogenesis 34, 1551-1557 (2013). 19. Braakhuis B. J.M., Tabor, M. P., Kummer, J. A., Leemans, C. R. & Brakenhoff, R. H. A genetic explanation of Slaughter’s concept of field cancerization: evidence and clinical implications.Cancer Res. 63, 1727-1730 (2003). 20. Girish, V.et al.Oncogene-like addiction to aneuploidy in human cancers.Science 381, eadg4521 (2023). 21. Chang, J.et al.Genomic analysis of oesophageal squamous-cell carcinoma identifies alcohol drinking-related mutation signature and genomic alterations.Nat. Commun. 8, 15290(2017). 22. Cancer Genome Atlas Network. Comprehensive genomic characterization of head and neck squamous cell carcinomas.Nature 517, 576-582 (2015). 23. Martinez, V. D.et al.Arsenic-related DNA copy-number alterations in lung squamous cell carcinomas.Br. J. Cancer 103, 1277-1283 (2010). 24. Stransky, N.et al.The mutational landscape of head and neck squamous cell carcinoma.Science 333, 1157-1160 (2011). 25. López de Cicco, R., Watson, J. C., Bassi, D. E., Litwin, S. & Klein-Szanto, A. J. Simultaneous expression of furin and vascular endothelial growth factor in human oral tongue squamous cell carcinoma progression.Clin. Cancer Res. 10, 4480-4488 (2004). 26. Choi S.& Thomson, P. Multiple oral cancer development—clinico‐pathological features in the Hong Kong population.J. Oral Pathol. Med. 49, 145-149 (2020). 27. Jovanovic, A.et al.Risk of multiple primary tumors following oral squamous-cell carcinoma.Int. J. Cancer 56, 320-323 (1994). 28. Tanjak, P.et al.Risks and cancer associations of metachronous and synchronous multiple primary cancers: a 25-year retrospective study.BMC Cancer 21, 1045(2021). 29. Pentenero M., Meleti M., Vescovi P.& Gandolfo, S. Oral proliferative verrucous leucoplakia: are there particular features for such an ambiguous entity? A systematic review.Br. J. Dermatol. 170, 1039-1047 (2014). 30. Qaisi M., Vorrasi J., Lubek J.& Ord, R. Multiple primary squamous cell carcinomas of the oral cavity.J. Oral Maxillofac. Surg. 72, 1511-1516 (2014). 31. Zhang, W.et al.Susceptibility of multiple primary cancers in patients with head and neck cancer: nature or nurture?Front. Oncol. 9, 1275(2019). 32. Li, K.et al.Preliminary study on the molecular features of mutation in multiple primary oral cancer by whole exome sequencing.Front. Oncol. 12, 971546(2022). 33. Cai, X.et al.Clinical and prognostic features of multiple primary cancers with oral squamous cell carcinoma.Arch. Oral. Biol. 149, 105661(2023). 34. Adebonojo, S. A., Moritz, D. M.& Danby, C. A. The results of modern surgical therapy for multiple primary lung cancers.Chest 112, 693-701 (1997). 35. Piñol, V.et al.Synchronous colorectal neoplasms in patients with colorectal cancer: predisposing individual and familial factors.Dis. Colon Rectum 47, 1192-1200 (2004). 36. Samadder, N. J.et al. Epidemiology and familial risk of synchronous and metachronous colorectal cancer: a population-based study in Utah. Clin. Gastroenterol. Hepatol. 12, 2078-2084.e2 (2014). 37. Pajares J. A.& Perea, J. Multiple primary colorectal cancer: individual or familial predisposition?World J. Gastrointest. Oncol. 7, 434(2015). 38. Chang, Y.-L.et al.Clonality and prognostic implications of p53 and epidermal growth factor receptor somatic aberrations in multiple primary lung cancers.Clin. Cancer Res. 13, 52-58 (2007). 39. Chiang, C.-L.et al.Recent advances in the diagnosis and management of multiple primary lung cancer.Cancers 14, 242(2022). 40. Rosin, M. P.et al.3p14 and 9p21 loss is a simple tool for predicting second oral malignancy at previously treated oral cancer sites.Cancer Res. 62, 6447-6450 (2002). 41. Naito, A.et al.RFPL4A increases the G1 population and decreases sensitivity to chemotherapy in human colorectal.Cancer Cells J. Biol. Chem. 290, 6326-6337 (2015). 42. Wang Y., Ledet R. J., Imberg-Kazdan, K., Logan, S. K. & Garabedian, M. J. Dynein axonemal heavy chain 8 promotes androgen receptor activity and associates with prostate cancer progression.Oncotarget 7, 49268-49280 (2016). 43. Zardab M., Stasinos K., Grose R. P.& Kocher, H. M. The obscure potential of AHNAK2.Cancers 14, 528(2022). 44. Zheng L., Li S., Zheng X., Guo R.& Qu, W. AHNAK2 is a novel prognostic marker and correlates with immune infiltration in papillary thyroid cancer: evidence from integrated analysis.Int. Immunopharmacol. 90, 107185(2021). 45. Kim, M. J.et al.CXCL16 positively correlated with M2-macrophage infiltration, enhanced angiogenesis, and poor prognosis in thyroid cancer.Sci. Rep. 9, 13288(2019). 46. Zheng, M.et al.Correlation between prognostic indicator AHNAK2 and immune infiltrates in lung adenocarcinoma.Int. Immunopharmacol. 90, 107134(2021). 47. Wang, W.et al.USP35 mitigates endoplasmic reticulum stress‐induced apoptosis by stabilizing RRBP1 in non‐small cell lung cancer.Mol. Oncol. 16, 1572-1590 (2022). 48. He, Y.et al.High glucose may promote the proliferation and metastasis of hepatocellular carcinoma via E2F1/RRBP1 pathway.Life Sci. 252, 117656(2020). 49. Shriwas, O.et al.RRBP1 rewires cisplatin resistance in oral squamous cell carcinoma by regulating Hippo pathway.Br. J. Cancer 124, 2004-2016 (2021). 50. Wang, X.et al.Evidence for common clonal origin of multifocal lung cancers.J. Natl Cancer Inst. 101, 560-570 (2009). 51. Hodges, K. B.et al.Clonal origin of multifocal hepatocellular carcinoma.Cancer 116, 4078-4085 (2010). 52. Ba, Y.et al.Case report: targeted sequencing improves the diagnosis of multiple synchronous lung cancers.Transl. Lung Cancer Res. 12, 933-939 (2023). 53. Scholes, A. G.et al.Synchronous oral carcinomas: independent or common clonal origin?Cancer Res. 58, 2003-2006 (1998). 54. Rohde, M.et al.Definition of locally recurrent head and neck squamous cell carcinoma: a systematic review and proposal for the Odense-Birmingham definition.Eur. Arch. Otorhinolaryngol. 277, 1593-1599 (2020). 55. Huang S. H.& O’Sullivan, B. Overview of the 8th edition TNM classification for head and neck cancer.Curr. Treat. Options Oncol. 18, 40(2017). 56. Li, X.et al.Improvement in the risk assessment of oral leukoplakia through morphology-related copy number analysis.Sci. China Life Sci. 64, 1379-1391 (2021). 57. Saunders, C. T.et al.Strelka: accurate somatic small-variant calling from sequenced tumor-normal sample pairs.Bioinformatics 28, 1811-1817 (2012). 58. Li H.& Durbin, R. Fast and accurate long-read alignment with Burrows-Wheeler transform.Bioinformatics 26, 589-595 (2010). 59. Faust G. G.& Hall, I. M.SAMBLASTER: fast duplicate marking and structural variant read extraction. Bioinformatics 30, 2503-2505 (2014). 60. Li, H.et al.The sequence alignment/map format and SAMtools.Bioinformatics 25, 2078-2079 (2009). 61. Cibulskis, K.et al.Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples.Nat. Biotechnol. 31, 213-219 (2013). 62. Kanehisa M.KEGG: kyoto encyclopedia of genes and genomes.Nucleic Acids Res. 28, 27-30 (2000). 63. Wang, K., Li, M.& Hakonarson, H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data.Nucleic Acids Res. 38, e164-e164 (2010). 64. Dees, N. D.et al.MuSiC: identifying mutational significance in cancer genomes.Genome Res. 22, 1589-1598 (2012). 65. Zhou, Y.et al.TTD: Therapeutic Target Database describing target druggability information.Nucleic Acids Res. 52, D1465-D1477 (2024).
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