title: Copy number alterations of chromosomal regions enclosing protein tyrosine phosphatase receptor-like genes in colorectal cancer.
abstract: Protein tyrosine phosphatases that act in different cellular pathways are described most commonly as tumor suppressors, but also as oncogenes. Their role has previously been described in colorectal cancer, as well as in gastric, breast, thyroid, prostate, ovarian, pancreatic, glioma, liver, leukemia and many other cancers. In a previous study, we have described protein tyrosine phosphatase receptor type T, M, Z1 and Q genes (PTPRT, PTPRM, PTPRZ1 and PTPRQ) hypermethylated in sporadic colorectal cancer. Thus, in this study, we examined the relation of unbalanced chromosomal alterations within regions covering these four protein tyrosine phosphatase genes with this cancer. One hundred and two cancer tissues were molecularly characterized, including analysis of the BRAF and K-ras mutations and methylator phenotype. The analysis of chromosomal aberrations was performed using Comparative Genomic Hybridization. We observed amplification of three regions containing genes coding for PTPs, such as PTPRZ1 (7q31.3, amplified in 23.5% of cases), PTPRQ (12q21.2, amplified in 5.9% of cases), PTPRT (20q12, amplified in 29.4% of cases), along with deletions in the region of PTPRM (18p11.2, deleted in 21.6% of cases). These data may suggest that in sporadic colorectal cancer PTPRZ1, PTPRT, PTPRQ probably act as oncogenes, while PTPRM acts as a tumor suppressor gene. Our study also revealed that gains on chromosome 20q12 and losses on chromosome 18p11.2 are connected with the absence of the BRAF mutation and the conventional adenocarcinoma pathway.
authors.affiliation: Genetics Department, Wroclaw Medical University, Wroclaw, Poland. Electronic address: izabela.laczmanska@umed.wroc.pl.
authors.forename: Izabela
authors.initials: I
authors.lastname: Laczmanska
authors.affiliation: Genetics Department, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Pawel
authors.initials: P
authors.lastname: Karpinski
authors.affiliation: Genetics Department, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Kozlowska
authors.affiliation: 1st Department of Surgical Oncology, Lower Silesian Oncology Center, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Bebenek
authors.affiliation: Department of Computer Science and Management, Wroclaw University of Technology, Poland.
authors.forename: David
authors.initials: D
authors.lastname: Ramsey
authors.affiliation: 1st Department of Surgical Oncology, Lower Silesian Oncology Center, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Sedziak
authors.affiliation: Department of Pathology, Wrocław Medical University, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Ziolkowski
authors.affiliation: Genetics Department, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Sasiadek
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002887:Chromosomes, Human, Pair 18; D002890:Chromosomes, Human, Pair 20; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D005260:Female; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D054557:Receptor-Like Protein Tyrosine Phosphatases / Q000235:genetics*; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000235:genetics; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000235:genetics; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C516859:PTPRM protein, human; C516917:PTPRQ protein, human; C516865:PTPRT protein, human; C516895:PTPRZ1 protein, human; D054557:Receptor-Like Protein Tyrosine Phosphatases; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: Colorectal cancer; Protein tyrosine phosphatase