title: Loss of PTPRM associates with the pathogenic development of colorectal adenoma-carcinoma sequence.
abstract: 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.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC.
authors.forename: Putty-Reddy
authors.initials: PR
authors.lastname: Sudhir
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC.
authors.forename: Shiu-Ting
authors.initials: ST
authors.lastname: Lin
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC.
authors.forename: Chien
authors.initials: C
authors.lastname: Chia-Wen
authors.affiliation: Department of Surgery, Taipei Veterans General Hospital, Taiwan, ROC.
authors.forename: Shung-Haur
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Department of Pathology, Taipei Veterans General Hospital, Taiwan, ROC.
authors.forename: Anna Fen-Yau
authors.initials: AF
authors.lastname: Li
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC.
authors.forename: Rai-Hua
authors.initials: RH
authors.lastname: Lai
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC.
authors.forename: Mei-Jung
authors.initials: MJ
authors.lastname: Wang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC.
authors.forename: Yuan-Tsong
authors.initials: YT
authors.lastname: Chen
authors.affiliation: VYM Genome Research Center, Taiwan, ROC.
authors.forename: Chian-Feng
authors.initials: CF
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC.
authors.forename: Yuh-Shan
authors.initials: YS
authors.lastname: Jou
authors.affiliation: 1] Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC [2] Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Jeou-Yuan
authors.initials: JY
authors.lastname: Chen
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D056915:DNA Copy Number Variations; D019175:DNA Methylation; D030541:Databases, Genetic; D015536:Down-Regulation; D005838:Genotype; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D019656:Loss of Heterozygosity; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; C516859:PTPRM protein, human; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2