The genomic landscape of undifferentiated embryonal sarcoma of the liver is typified by C19MC structural rearrangement and overexpression combined with TP53 mutation or loss.
PLoS Genet
; 16(4): e1008642, 2020 04.
Article
en En
| MEDLINE
| ID: mdl-32310940
ABSTRACT
Undifferentiated embryonal sarcoma of the liver (UESL) is a rare and aggressive malignancy. Though the molecular underpinnings of this cancer have been largely unexplored, recurrent chromosomal breakpoints affecting a noncoding region on chr19q13, which includes the chromosome 19 microRNA cluster (C19MC), have been reported in several cases. We performed comprehensive molecular profiling on samples from 14 patients diagnosed with UESL. Congruent with prior reports, we identified structural variants in chr19q13 in 10 of 13 evaluable tumors. From whole transcriptome sequencing, we observed striking expressional activity of the entire C19MC region. Concordantly, in 7 of 7 samples undergoing miRNAseq, we observed hyperexpression of the miRNAs within this cluster to levels >100 fold compared to matched normal tissue or a non-C19MC amplified cancer cell line. Concurrent TP53 mutation or copy number loss was identified in all evaluable tumors with evidence of C19MC overexpression. We find that C19MC miRNAs exhibit significant negative correlation to TP53 regulatory miRNAs and K-Ras regulatory miRNAs. Using RNA-seq we identified that pathways relevant to cellular differentiation as well as mRNA translation machinery are transcriptionally enriched in UESL. In summary, utilizing a combination of next-generation sequencing and high-density arrays we identify the combination of C19MC hyperexpression via chromosomal structural event with TP53 mutation or loss as highly recurrent genomic features of UESL.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Sarcoma
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Cromosomas Humanos Par 19
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Regulación Neoplásica de la Expresión Génica
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Proteína p53 Supresora de Tumor
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Neoplasias de Células Germinales y Embrionarias
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MicroARNs
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Puntos de Rotura del Cromosoma
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Neoplasias Hepáticas
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Mutación
Límite:
Child
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Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
PLoS Genet
Asunto de la revista:
GENETICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos