oral squamous cell carcinoma
ARTICLE
Received 6 Sep 2013 | Accepted 5 Nov 2013 | Published 2 Dec 2013
DOI: 10.1038/ncomms3873
OPEN
Mutational landscape of gingivo-buccal oral squamous cell carcinoma reveals new recurrently-mutated genes and molecular subgroups India Project Team of the International Cancer Genome Consortium1
Gingivo-buccal oral squamous cell carcinoma (OSCC-GB), an anatomical and clinical subtype of head and neck squamous cell carcinoma (HNSCC), is prevalent in regions where tobaccochewing is common. Exome sequencing (n ¼ 50) and recurrence testing (n ¼ 60) reveals that some significantly and frequently altered genes are specific to OSCC-GB (USP9X, MLL4,
ARID2, UNC13C and TRPM3), while some others are shared with HNSCC (for example, TP53,
FAT1, CASP8, HRAS and NOTCH1). We also find new genes with recurrent amplifications
(for example, DROSHA, YAP1) or homozygous deletions (for example, DDX3X) in OSCC-GB.
We find a high proportion of C4G transversions among tobacco users with high numbers of mutations. Many pathways that are enriched for genomic alterations are specific to
OSCC-GB. Our work reveals molecular subtypes with distinctive mutational profiles such as patients predominantly harbouring mutations in CASP8 with or without mutations in FAT1.
Mean duration of disease-free survival is significantly elevated in some molecular subgroups.
These findings open new avenues for biological characterization and exploration of therapies.
.Correspondence and requests for materials should be addressed to P.P.M. (email: ppm1@nibmg.ac.in) or to R.S. (email: rsarin@actrec.gov.in).
1A full list of India Project Team of the International Cancer Genome Consortium and their affiliations appears at the end of the paper.
NATURE COMMUNICATIONS | 4:2873 | DOI: 10.1038/ncomms3873 | www.nature.com/naturecommunications
& 2013 Macmillan Publishers Limited. All rights reserved.
1
ARTICLE
NATURE COMMUNICATIONS | DOI: 10.1038/ncomms3873
O
ral squamous cell
Received 6 Sep 2013 | Accepted 5 Nov 2013 | Published 2 Dec 2013
DOI: 10.1038/ncomms3873
OPEN
Mutational landscape of gingivo-buccal oral squamous cell carcinoma reveals new recurrently-mutated genes and molecular subgroups India Project Team of the International Cancer Genome Consortium1
Gingivo-buccal oral squamous cell carcinoma (OSCC-GB), an anatomical and clinical subtype of head and neck squamous cell carcinoma (HNSCC), is prevalent in regions where tobaccochewing is common. Exome sequencing (n ¼ 50) and recurrence testing (n ¼ 60) reveals that some significantly and frequently altered genes are specific to OSCC-GB (USP9X, MLL4,
ARID2, UNC13C and TRPM3), while some others are shared with HNSCC (for example, TP53,
FAT1, CASP8, HRAS and NOTCH1). We also find new genes with recurrent amplifications
(for example, DROSHA, YAP1) or homozygous deletions (for example, DDX3X) in OSCC-GB.
We find a high proportion of C4G transversions among tobacco users with high numbers of mutations. Many pathways that are enriched for genomic alterations are specific to
OSCC-GB. Our work reveals molecular subtypes with distinctive mutational profiles such as patients predominantly harbouring mutations in CASP8 with or without mutations in FAT1.
Mean duration of disease-free survival is significantly elevated in some molecular subgroups.
These findings open new avenues for biological characterization and exploration of therapies.
.Correspondence and requests for materials should be addressed to P.P.M. (email: ppm1@nibmg.ac.in) or to R.S. (email: rsarin@actrec.gov.in).
1A full list of India Project Team of the International Cancer Genome Consortium and their affiliations appears at the end of the paper.
NATURE COMMUNICATIONS | 4:2873 | DOI: 10.1038/ncomms3873 | www.nature.com/naturecommunications
& 2013 Macmillan Publishers Limited. All rights reserved.
1
ARTICLE
NATURE COMMUNICATIONS | DOI: 10.1038/ncomms3873
O
ral squamous cell
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