Differential gene expression profiling of primary cutaneous melanoma and sentinel lymph node metastases.
Mod Pathol
; 25(6): 828-37, 2012 Jun.
Article
en En
| MEDLINE
| ID: mdl-22411186
ABSTRACT
Limited understanding of molecular mechanisms of metastasis in melanoma contributes to the absence of effective treatments. Increased knowledge of alterations in genes that underpin critical molecular events that lead to metastasis is essential. We have investigated the gene expression profiles of primary melanomas and melanoma metastases in sentinel lymph nodes. A total of 19 samples (10 primary melanomas and 9 sentinel lymph node metastases) were evaluated. Melanoma cells were dissected from tissue blocks. Total mRNA was isolated, amplified, and labeled using an Ambion Recover All Total Nucleic Acid Isolation kit, Nu-GEN WT-Ovation formalin-fixed, paraffin-embedded RNA Amplification System, and FL-Ovation cDNA Biotin Module V2, respectively. Samples were hybridized to the Affymetrix Gene Chip Human U133 Plus 2.0 Array. Data were analyzed using Partek Genomics Suite Version 6.4. Genes selected showed ≥2-fold difference in expression and P<5.00E-2. Validation studies used standard immunohistochemical assays. Hierarchical clustering disclosed two distinct groups 10 primary melanomas and 9 sentinel lymph node metastases. Gene expression analysis identified 576 genes that showed significant differential expression. Most differences reflected decreased gene expression in metastases relative to primaries. Reduced gene expression in primaries was less frequent and less dramatic. Genes significantly increased or decreased in sentinel lymph node metastases were active in cell adhesion/structural integrity, tumor suppression, cell cycle regulation, and apoptosis. Validation studies indicate that MAGEC1 (melanoma antigen family C1) and FCRL1 (Fc receptor-like 1) are involved in melanoma progression. There are striking differential gene expression patterns between primary and nodally metastatic melanomas. Similar findings were seen with autologous paired primary melanomas and sentinel lymph node metastases, supporting involvement of these gene alterations in evolution of metastases. With further study, it may be possible to determine the exact sequence of molecular events that underlie melanoma metastases.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Cutáneas
/
Biomarcadores de Tumor
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Perfilación de la Expresión Génica
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Ganglios Linfáticos
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Melanoma
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
Límite:
Adult
/
Aged
/
Aged80
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Female
/
Humans
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Male
/
Middle aged
País/Región como asunto:
America do norte
/
Oceania
Idioma:
En
Revista:
Mod Pathol
Asunto de la revista:
PATOLOGIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA