Chromosome 5q loss in colorectal flat adenomas
Menée sur des échantillons d'adénomes colorectaux (85 de type "plan", 35 de type "polyploïde"), cette étude met en évidence des altérations génomiques spécifiques aux adénomes plans, notamment la perte du chromosome 5q
Purpose Flat adenomas are a subgroup of colorectal adenomas that have been associated with a more aggressive clinical behavior compared to their polypoid counterparts. Here, we aimed to compare one of the molecular changes most explicitly associated with adenoma to carcinoma progression, i.e. chromosomal instability, between flat and polypoid colorectal adenomas. Experimental Design Consecutive series of 83 flat and 35 polypoid adenomas were analyzed for DNA copy number changes using a high-resolution arrayCGH platform, microsatellite instability (MSI) status and for mutations in the adenomatous polyposis coli (APC) gene. Immunohistochemical stainings for CD3, CD8 and FoxP3 expression were performed. Results Patterns of DNA copy number changes differed between the two phenotypes with significantly more frequent loss of 5q14.3 and 5q15-q31.1 in flat adenomas, while losses of 1p36.32-p35.3, 10q25.3, 17p12 and chromosome 18 were more frequent in polypoid adenomas (FDR less than 0.2). MSI was observed in one flat adenoma. As the 5q15-q31.1 region harbors the APC locus, APC mutation status was investigated, showing significantly less mutations in flat adenomas (p=0.04). An initial exploration of a possible association of 5q loss with inflammation indicated that tumor infiltrating lymphocytes were more abundant in the stroma of flat adenomas compared to that of polypoid adenomas. Conclusion Flat and polypoid adenomas have partially distinct chromosomal profiles, consistent with differences in the biology underlying these phenotypes. Alterations more specific to flat adenomas, in particular 5q loss, may be associated with inflammation.