Concurrent MCL1 and JUN amplification in pseudomyxoma peritonei: a comprehensive genetic profiling and survival analysis.
J Hum Genet
; 59(3): 124-8, 2014 Mar.
Article
em En
| MEDLINE
| ID: mdl-24369359
ABSTRACT
Pseudomyxoma peritonei (PMP) is a rare abdominal malignancy. We hypothesized that next-generation exomic sequencing would identify recurrent mutations that may have prognostic or therapeutic implications. Ten patients were selected on the basis of availability of tissue and adequate follow-up. They were treated at our institution between September 2002 and August 2004. Using next-generation exomic sequencing, we tested for mutations in 236 cancer-related genes in formalin-fixed paraffin-embedded slides. MCL1 amplification was additionally tested with immunohistochemical staining. Detectable mutations were found in 8 patients (80%). Seven patients harbored a KRAS mutation, most commonly involving codon 12. Four GNAS mutations (R201H/R201C substitutions) were also detected. MCL1 and JUN were concurrently amplified in three patients. One patient with MCL1 and JUN amplification had concurrent amplification of MYC and NFKBIA. ZNF703 was amplified in one patient. Patients with MCL1 amplification were also found to express MCL1 with immunohistochemistry, but MCL1 expression was also detected in some patients without amplification. To our knowledge, we are the first to report MCL1 and JUN coamplification in PMP. Expression of MCL1 may not be completely dependent on amplification. The prognostic and therapeutic implications of these recurrent mutational events are the subject of ongoing investigation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pseudomixoma Peritoneal
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Amplificação de Genes
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Proteínas Proto-Oncogênicas c-jun
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Perfilação da Expressão Gênica
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Proteína de Sequência 1 de Leucemia de Células Mieloides
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Hum Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos