Epigenetic silencing of NTSR1 is associated with lateral and noninvasive growth of colorectal tumors

Oncotarget
Seiko KamimaeHiromu Suzuki

Abstract

Our aim was to identify DNA methylation changes associated with the growth pattern and invasiveness of colorectal cancers (CRCs). Comparison of the methylation statuses of large (≥ 20 mm in diameter along the colonic surface) noninvasive tumors (NTs) and small (<20 mm in diameter along the colonic surface) invasive tumors (ITs) using CpG island microarray analysis showed neurotensin receptor 1 (NTSR1) to be hypermethylated in large NTs. Quantitative bisulfite pyrosequencing revealed that NTSR1 is frequently methylated in colorectal tumors, with large NTs exhibiting the highest methylation levels. The higher NTSR1 methylation levels were associated with better prognoses. By contrast, NTSR1 copy number gains were most frequent among small ITs. Methylation of NTSR1 was associated with the gene's silencing in CRC cell lines, whereas ectopic expression of NTSR1 promoted proliferation and invasion by CRC cells. Analysis of primary tumors composed of adenomatous and malignant portions revealed that NTSR1 is frequently methylated in the adenomatous portion, while methylation levels are generally lower in the cancerous portions. These results suggest that NTSR1 methylation is associated with lateral and noninvasive growth of colorectal ...Continue Reading

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Methods Mentioned

BETA
methylation profiling
ChIP-PCR
chromosomal aberrations
immunoprecipitation
biopsy
xenografts
surgical resection
surgical
dissection
Feature Extraction

Software Mentioned

GeneSpring GX
CpG
GraphPad Prism
FlowJo
Feature Extraction

Related Concepts