Dataset Information

Analysis of chromosomal aberration (1, 3, and 8) and association of microRNAs in uveal melanoma.

ABSTRACT: PURPOSE: Uveal melanoma is the most common intraocular primary tumor, involving iris, ciliary body and choroid. More than 90% of the patients develop hepatic metastasis with an average survival time of 7 months. We have used formalin fixed paraffin embedded sections to validate the presence of monosomy 3, an accurate predictor of metastasis, chromosome 8 isochromosome (8q22), and 1p36 deletion. This study also tested the presence of oncomirs in uveal melanoma samples by microRNA (miRNA) expression profiling. METHODS: Chromogenic in situ hybridization (CISH) was performed in formalin fixed, paraffin embedded sections of uveal melanoma to analyze chromosome 1, 3, and 8 aberrations (n=60). MicroRNA (miRNA) expression profiling was done on paraffin sections of invasive tumor with liver metastasis (n=1) and non invasive tumor (n=1) in biological duplicates. Samples for miRNA expression profiling were identified based on case registry and the harboring of monosomy 3 by CISH. RESULTS: A significant correlation (p=0.05) between metastasizing and non-metastasizing melanoma harboring chromosomal aberrations- monosomy3, c-myc, and 1p36 was observed by Pearson's correlation. A significant correlation was observed in monosomy 3 and 1p36 positive cases in the tumor samples (p=0.039). No significance was observed between monosomy 3 and c-myc positive cases. No significance (p=0.096) was observed between c-myc amplification and trisomy (extra whole chromosome 8). MicroRNA expression profiling revealed the presence of 19 miRNAs expressed in non-metastasizing melanoma and absent in metastasizing melanoma. Eleven miRNAs were found to be expressed in metastasizing melanoma and absent in non-metastasizing melanoma. Genes targeted by the miRNAs were found to be present in chromosomal regions 8p22, 13q, and 17p but were often found to be deleted. CONCLUSIONS: This technique can be applied to routine pathology using archival specimens to identify patients with monosomy 3. We were able to perform CISH in all the cases except the heavily pigmented tumors, where dots were observed but were not assessed. Initial studies on microRNA have revealed their role as oncomirs in both metastasizing and non-metastasizing melanomas. Further studies may provide insights into their role in tumor progression and facilitate metastatic phenotype analysis.

SUBMITTER: Radhakrishnan A

PROVIDER: S-EPMC2773734 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Analysis of chromosomal aberration (1, 3, and 8) and association of microRNAs in uveal melanoma.

Radhakrishnan Abhirami A Badhrinarayanan Nirmala N Biswas Jyotirmay J Krishnakumar Subramanian S

Molecular vision 20091022

<h4>Purpose</h4>Uveal melanoma is the most common intraocular primary tumor, involving iris, ciliary body and choroid. More than 90% of the patients develop hepatic metastasis with an average survival time of 7 months. We have used formalin fixed paraffin embedded sections to validate the presence of monosomy 3, an accurate predictor of metastasis, chromosome 8 isochromosome (8q22), and 1p36 deletion. This study also tested the presence of oncomirs in uveal melanoma samples by microRNA (miRNA) e ...[more]

PMID: 19898689

Similar Datasets

Project description:The profound disparity in response to immune checkpoint blockade (ICB) by cutaneous melanoma (CM) and uveal melanoma (UM) patients is not well understood. Therefore, we characterized metastases of CM and UM from the same metastatic site (liver), in order to dissect the potential underlying mechanism in differential response on ICB. Tumor liver samples from CM (n=38) and UM (n=28) patients were analyzed at the genomic (whole exome sequencing), transcriptional (RNA sequencing) and protein (immunohistochemistry and GeoMx Digital Spatial Profiling) level. Comparison of CM and UM metastases from the same metastatic site revealed that, although originating from the same melanocyte lineage, CM and UM differed in somatic mutation profile, copy number profile, tumor mutational burden (TMB) and consequently predicted neoantigens. A higher melanin content and higher expression of the melanoma differentiation antigen MelanA was observed in liver metastases of UM patients. No difference in B2M and human leukocyte antigen-DR (HLA-DR) expression was observed. A higher expression of programmed cell death ligand 1 (PD-L1) was found in CM compared with UM liver metastases, although the majority of CM and UM liver metastases lacked PD-L1 expression. There was no difference in the extent of immune infiltration observed between CM and UM metastases, with the exception of a higher expression of CD163 (p<0.0001) in CM liver samples. While the extent of immune infiltration was similar for CM and UM metastases, the ratio of exhausted CD8 T cells to cytotoxic T cells, to total CD8 T cells and to Th1 cells, was significantly higher in UM metastases. While TMB was different between CM and UM metastases, tumor immune infiltration was similar. The greater dependency on PD-L1 as an immune checkpoint in CM and the identification of higher exhaustion ratios in UM may both serve as explanations for the difference in response to ICB. Consequently, in order to improve current treatment for metastatic UM, reversal of T cell exhaustion beyond programmed cell death 1 blockade should be considered.

Dataset Information

Analysis of chromosomal aberration (1, 3, and 8) and association of microRNAs in uveal melanoma.

Publications

Analysis of chromosomal aberration (1, 3, and 8) and association of microRNAs in uveal melanoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets