Whole-genome sequencing of an aggressive BRAF wild-type papillary thyroid cancer identified EML4-ALK translocation as a therapeutic target.
World J Surg
; 38(6): 1296-305, 2014 Jun.
Article
em En
| MEDLINE
| ID: mdl-24633422
ABSTRACT
BACKGROUND:
Recent advances in the treatment of cancer have focused on targeting genomic aberrations with selective therapeutic agents. In radioiodine resistant aggressive papillary thyroid cancers, there remain few effective therapeutic options. A 62-year-old man who underwent multiple operations for papillary thyroid cancer and whose metastases progressed despite standard treatments provided tumor tissue.METHODS:
We analyzed tumor and whole blood DNA by whole genome sequencing, achieving 80× or greater coverage over 94 % of the exome and 90 % of the genome. We determined somatic mutations and structural alterations.RESULTS:
We found a total of 57 somatic mutations in 55 genes of the cancer genome. There was notably a lack of mutations in NRAS and BRAF, and no RET/PTC rearrangement. There was a mutation in the TRAPP oncogene and a loss of heterozygosity of the p16, p18, and RB1 tumor suppressor genes. The oncogenic driver for this tumor is a translocation involving the genes for anaplastic lymphoma receptor tyrosine kinase (ALK) and echinoderm microtubule associated protein like 4 (EML4). The EML4-ALK translocation has been reported in approximately 5 % of lung cancers, as well as in pediatric neuroblastoma, and is a therapeutic target for crizotinib.CONCLUSIONS:
This is the first report of the whole genomic sequencing of a papillary thyroid cancer in which we identified an EML4-ALK translocation of a TRAPP oncogene mutation. These findings suggest that this tumor has a more distinct oncogenesis than BRAF mutant papillary thyroid cancer. Whole genome sequencing can elucidate an oncogenic context and expose potential therapeutic vulnerabilities in rare cancers.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
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Piridinas
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Neoplasias da Glândula Tireoide
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Serina Endopeptidases
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Carcinoma
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Receptores Proteína Tirosina Quinases
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Proteínas de Ciclo Celular
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Proteínas Associadas aos Microtúbulos
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Recidiva Local de Neoplasia
Tipo de estudo:
Etiology_studies
/
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article