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Loss of PTPRM associates with the pathogenic development of colorectal adenoma-carcinoma sequence.

Publication ,  Journal Article
Sudhir, P-R; Lin, S-T; Chia-Wen, C; Yang, S-H; Li, AF-Y; Lai, R-H; Wang, M-J; Chen, Y-T; Chen, C-F; Jou, Y-S; Chen, J-Y
Published in: Sci Rep
April 24, 2015

Identification and functional analysis of genes from genetically altered chromosomal regions would suggest new molecular targets for cancer diagnosis and treatment. Here we performed a genome-wide analysis of chromosomal copy number alterations (CNAs) in matching sets of colon mucosa-adenoma-carcinoma samples using high-throughput oligonucleotide microarray analysis. In silico analysis of NCBI GEO and TCGA datasets allowed us to uncover the significantly altered genes (p ≤ 0.001) associated with the identified CNAs. We performed quantitative PCR analysis of the genomic and complementary DNA derived from primary mucosa, adenoma, and carcinoma samples, and confirmed the recurrent loss and down-regulation of PTPRM in colon adenomas and carcinomas. Functional characterization demonstrated that PTPRM negatively regulates cell growth and colony formation, whereas loss of PTPRM promotes oncogenic cell growth. We further showed that, in accordance to Knudson's two-hit hypothesis, inactivation of PTPRM in colon cancer was mainly attributed to loss of heterozygosity and promoter hypermethylation. Taken together, this study demonstrates a putative tumor suppressive role for PTPRM and that genetic and epigenetic alterations of PTPRM may contribute to early step of colorectal tumorigenesis.

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Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

April 24, 2015

Volume

5

Start / End Page

9633

Location

England

Related Subject Headings

  • Receptor-Like Protein Tyrosine Phosphatases, Class 2
  • Real-Time Polymerase Chain Reaction
  • RNA, Small Interfering
  • RNA Interference
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Oligonucleotide Array Sequence Analysis
  • Loss of Heterozygosity
  • Intestinal Mucosa
  • Humans
 

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Sudhir, P.-R., Lin, S.-T., Chia-Wen, C., Yang, S.-H., Li, A.-Y., Lai, R.-H., … Chen, J.-Y. (2015). Loss of PTPRM associates with the pathogenic development of colorectal adenoma-carcinoma sequence. Sci Rep, 5, 9633. https://doi.org/10.1038/srep09633
Sudhir, Putty-Reddy, Shiu-Ting Lin, Chien Chia-Wen, Shung-Haur Yang, Anna Fen-Yau Li, Rai-Hua Lai, Mei-Jung Wang, et al. “Loss of PTPRM associates with the pathogenic development of colorectal adenoma-carcinoma sequence.Sci Rep 5 (April 24, 2015): 9633. https://doi.org/10.1038/srep09633.
Sudhir P-R, Lin S-T, Chia-Wen C, Yang S-H, Li AF-Y, Lai R-H, et al. Loss of PTPRM associates with the pathogenic development of colorectal adenoma-carcinoma sequence. Sci Rep. 2015 Apr 24;5:9633.
Sudhir, Putty-Reddy, et al. “Loss of PTPRM associates with the pathogenic development of colorectal adenoma-carcinoma sequence.Sci Rep, vol. 5, Apr. 2015, p. 9633. Pubmed, doi:10.1038/srep09633.
Sudhir P-R, Lin S-T, Chia-Wen C, Yang S-H, Li AF-Y, Lai R-H, Wang M-J, Chen Y-T, Chen C-F, Jou Y-S, Chen J-Y. Loss of PTPRM associates with the pathogenic development of colorectal adenoma-carcinoma sequence. Sci Rep. 2015 Apr 24;5:9633.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

April 24, 2015

Volume

5

Start / End Page

9633

Location

England

Related Subject Headings

  • Receptor-Like Protein Tyrosine Phosphatases, Class 2
  • Real-Time Polymerase Chain Reaction
  • RNA, Small Interfering
  • RNA Interference
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Oligonucleotide Array Sequence Analysis
  • Loss of Heterozygosity
  • Intestinal Mucosa
  • Humans