Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of tumors from the melanoblastoma bearing Libechov Minipig (MeLiM) model at 8 to 91 days after birth


ABSTRACT: Spontaneous regression is a well defined phenomenon commonly observed in human melanoma in its partial histopathological form but sporadically in its complete expression. Molecular mechanisms which might be involved in spontaneous regression are poorly understood so far. The Melanoblastoma bearing Libechov Minipig (MeLiM) model exhibits cutaneous melanomas which appear in utero or shortly after birth. These lesions are clinically and histologically highly comparable to their human counterparts. Nevertheless, in swine most of the highly invasive melanomas undergo complete spontaneous regression. Induction of regression is expressed by clinical features including changes in color, drying aspect and decrease in size; histologically we observed infiltration of histiocyte-like cells, fibrosis and lymphocytic infiltrate later. To characterize the regression phase on a transciptomic level, we performed time dependent gene expression profiling using the MeLiM model and porcine Affymetrix microarrays. We collected 5 different tumors of 5 siblings at 5 timepoints, from day 8 to day 91 after birth. After statistical analysis and reannotation of the 25 porcine microarrays we were able to identify 1411 genes regulated during regression. K-means clustering and subsequent functional clustering of these genes via Ingenuity Pathway analysis revealed significant pathways playing a role in melanoma regression. Genes involved in cell cycle, apoptosis, cellular movement, melanocyte-differentiation and pigmentation as well as genes of the immune reponse seem to be potential mediators of melanoma regression.

ORGANISM(S): Sus scrofa

SUBMITTER: Sylvain Baulande 

PROVIDER: E-MEXP-1152 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Gene expression signature for spontaneous cancer regression in melanoma pigs.

Rambow Florian F   Piton Guillaume G   Bouet Stephan S   Leplat Jean-Jaques JJ   Baulande Sylvain S   Marrau Angelique A   Stam Mark M   Horak Vratislav V   Vincent-Naulleau Silvia S  

Neoplasia (New York, N.Y.) 20080701 7


Incomplete spontaneous regression of melanoma is common. However, complete melanoma regression is still a very rare phenomenon. Because melanoma is the most immunogenic human malignancy, the mechanisms leading to regression, based on accumulative evidence, are the host's immune responses. Unfortunately, therapies aiming to enhance the patient's natural immunity against melanoma have yet to meet their expectations. Reasons for failure include various immune escape mechanisms, induced by the tumor  ...[more]

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