Copy number variation: A prognostic marker for young patients with squamous cell carcinoma of the oral tongue.
age
copy number variation
prognosis
squamous cell carcinoma of the oral tongue
whole-exome sequencing
Journal
Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology
ISSN: 1600-0714
Titre abrégé: J Oral Pathol Med
Pays: Denmark
ID NLM: 8911934
Informations de publication
Date de publication:
Jan 2019
Jan 2019
Historique:
received:
16
10
2018
accepted:
17
10
2018
pubmed:
26
10
2018
medline:
18
5
2019
entrez:
26
10
2018
Statut:
ppublish
Résumé
The incidence of squamous cell carcinoma of the oral tongue (SCCOT) is increasing in people under age 40. There is an urgent need to identify prognostic markers that help identify young SCCOT patients with poor prognosis in order to select these for individualized treatment. To identify genetic markers that can serve as prognostic markers for young SCCOT patients, we first investigated four young (≤40 years) and five elderly patients (≥50 years) using global RNA sequencing and whole-exome sequencing. Next, we combined our data with data on SCCOT from the cancer genome atlas (TCGA), giving a total of 16 young and 104 elderly, to explore the correlations between genomic variations and clinical outcomes. In agreement with previous studies, we found that SCCOT from young and elderly patients was transcriptomically and also genomically similar with no significant differences regarding cancer driver genes, germline predisposition genes, or the burden of somatic single nucleotide variations (SNVs). However, a disparate copy number variation (CNV) was found in young patients with distinct clinical outcome. Combined with data from TCGA, we found that the overall survival was significantly better in young patients with low-CNV (n = 5) compared to high-CNV (n = 11) burden (P = 0.044). Copy number variation burden is a useful single prognostic marker for SCCOT from young, but not elderly, patients. CNV burden thus holds promise to form an important contribution when selecting suitable treatment protocols for young patients with SCCOT.
Sections du résumé
BACKGROUND
BACKGROUND
The incidence of squamous cell carcinoma of the oral tongue (SCCOT) is increasing in people under age 40. There is an urgent need to identify prognostic markers that help identify young SCCOT patients with poor prognosis in order to select these for individualized treatment.
MATERIALS AND METHODS
METHODS
To identify genetic markers that can serve as prognostic markers for young SCCOT patients, we first investigated four young (≤40 years) and five elderly patients (≥50 years) using global RNA sequencing and whole-exome sequencing. Next, we combined our data with data on SCCOT from the cancer genome atlas (TCGA), giving a total of 16 young and 104 elderly, to explore the correlations between genomic variations and clinical outcomes.
RESULTS
RESULTS
In agreement with previous studies, we found that SCCOT from young and elderly patients was transcriptomically and also genomically similar with no significant differences regarding cancer driver genes, germline predisposition genes, or the burden of somatic single nucleotide variations (SNVs). However, a disparate copy number variation (CNV) was found in young patients with distinct clinical outcome. Combined with data from TCGA, we found that the overall survival was significantly better in young patients with low-CNV (n = 5) compared to high-CNV (n = 11) burden (P = 0.044).
CONCLUSIONS
CONCLUSIONS
Copy number variation burden is a useful single prognostic marker for SCCOT from young, but not elderly, patients. CNV burden thus holds promise to form an important contribution when selecting suitable treatment protocols for young patients with SCCOT.
Identifiants
pubmed: 30357923
doi: 10.1111/jop.12792
pmc: PMC6587711
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
24-30Subventions
Organisme : Lion's Cancer Research Foundation
ID : 17 0663
Organisme : Czech Republic
ID : P206/12/G151
Organisme : Ministry of Education Youth and Sports in the Czech Republic
ID : MEYS-NPSI-LO1413
Informations de copyright
© 2018 The Authors. Journal of Oral Pathology & Medicine Published by John Wiley & Sons Ltd.
Références
Nature. 2015 Jan 29;517(7536):576-82
pubmed: 25631445
Nat Biotechnol. 2013 Mar;31(3):213-9
pubmed: 23396013
Nucleic Acids Res. 2016 Nov 16;44(20):e154
pubmed: 27507884
Nat Rev Genet. 2015 Mar;16(3):172-83
pubmed: 25645873
Cancer Discov. 2012 May;2(5):401-4
pubmed: 22588877
J Oral Pathol Med. 2019 Jan;48(1):24-30
pubmed: 30357923
Oral Oncol. 2017 Apr;67:146-152
pubmed: 28351569
Nat Genet. 2013 Oct;45(10):1134-40
pubmed: 24071852
Clin Cancer Res. 2014 Jul 15;20(14):3842-8
pubmed: 24874835
Nat Protoc. 2016 Sep;11(9):1650-67
pubmed: 27560171
BMC Cancer. 2016 May 26;16:335
pubmed: 27229929
Int J Cancer. 2002 Sep 1;101(1):95-9
pubmed: 12209594
Nat Commun. 2015 Dec 22;6:10086
pubmed: 26689913
Br J Cancer. 2015 Jun 9;112(12):1958-65
pubmed: 25973533
Genome Res. 2010 Sep;20(9):1297-303
pubmed: 20644199
Oral Oncol. 2001 Jul;37(5):401-18
pubmed: 11377229
Oral Maxillofac Surg Clin North Am. 2014 May;26(2):123-41
pubmed: 24794262
Cell Oncol. 2009;31(4):291-300
pubmed: 19633365
J Oral Pathol Med. 2018 Jul;47(6):541-546
pubmed: 28922483
Int J Epidemiol. 2015 Feb;44(1):169-85
pubmed: 25613428
Br J Cancer. 2015 Jul 14;113(2):321-6
pubmed: 26057450
Int J Cancer. 2016 Jan 1;138(1):98-109
pubmed: 26175310
J Clin Oncol. 2006 May 10;24(14):2137-50
pubmed: 16682732
Head Neck. 1994 Mar-Apr;16(2):107-11
pubmed: 8021128
Proc Natl Acad Sci U S A. 2016 Dec 13;113(50):14330-14335
pubmed: 27911828
Oral Oncol. 2009 Aug;45(8):e57-61
pubmed: 19362043
Cell. 2018 Apr 5;173(2):355-370.e14
pubmed: 29625052
J Oral Pathol Med. 2012 May;41(5):379-83
pubmed: 22084865
Oncogene. 2000 Nov 20;19(49):5590-7
pubmed: 11114739
Maxillofac Plast Reconstr Surg. 2017 Dec 25;39(1):41
pubmed: 29302590
Proc Natl Acad Sci U S A. 2014 Jul 29;111(30):11139-44
pubmed: 25024180