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Targeted sequencing of tonsillar and base of tongue cancer and human papillomavirus positive unknown primary of the head and neck reveals prognostic effects of mutated FGFR3
Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
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2017 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 21, p. 35339-35350Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Human papillomavirus positive (HPV+) tonsillar cancer (TSCC), base of tongue cancer (BOTSCC) and unknown primary cancer of the head and neck (HNCUP) have better outcome than corresponding HPV- cancers. To find predictive markers for response to treatment, and correlations and differences in mutated oncogenes and suppressor genes between HPV+ TSCC/BOTSSCC and HPV+ HNCUP and HPV- TSCC/BOTSCC targeted next-generation sequencing was performed of frequently mutated regions in 50 cancer related genes.

PATIENTS AND METHODS: DNA from 348 TSCC/BOTSCC and 20 HNCUP from patients diagnosed 2000-2011, was sequenced by the Ion Proton sequencing platform using the Ion AmpliSeq Cancer Hotspot Panel v2 to identify frequently mutated regions in 50 cancer related genes. Ion Torrent Variant Caller software was used to call variants.

RESULTS: 279 HPV+ TSCC/BOTSCC, 46 HPV- TSCC/BOTSCC and 19 HPV+ HNCUP samples qualified for further analysis. Mutations/tumor were fewer in HPV+ TSCC/BOTSCC and HNCUP, compared to HPV- tumors (0.92 vs. 1.32 vs. 1.68). Differences in mutation frequency of TP53 and PIK3CA were found between HPV+ TSCC/BOTSCC and HNCUP and HPV- TSCC/BOTSCC. In HPV+ TSCC/BOTSCC presence of FGFR3 mutations correlated to worse prognosis. Other correlations to survival within the groups were not disclosed.

CONCLUSIONS: In HPV+ TSCC/BOTSCC mutation of PIK3CA was most frequently observed, while TP53 mutations dominated in HPV- TSCC/BOTSCC. In HPV+ TSCC/ BOTSCC and HNCUP, mutations/tumor were similar in frequency and fewer compared to that in HPV- TSCC/BOTSCC. Notably, FGFR3 mutations in HPV+ TSCC/BOTSCC indicated worse prognosis.

Place, publisher, year, edition, pages
IMPACT JOURNALS LLC , 2017. Vol. 8, no 21, p. 35339-35350
Keywords [en]
HPV, tonsillar cancer, base of tongue cancer, cancer of unknown primary of the head and neck region, FGFR3 mutation
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-326237DOI: 10.18632/oncotarget.15240ISI: 000402051700117PubMedID: 28525363OAI: oai:DiVA.org:uu-326237DiVA, id: diva2:1120082
Funder
Swedish Cancer SocietyCancer and Allergy FoundationStockholm County CouncilSwedish National Infrastructure for Computing (SNIC), b2015372Available from: 2017-07-05 Created: 2017-07-05 Last updated: 2017-11-29Bibliographically approved

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