Laczmanska Izabela, Karpinski Pawel, Kozlowska Joanna, Bebenek Marek, Ramsey David, Sedziak Tomasz, Ziolkowski Piotr, Sasiadek Maria M
Genetics Department, Wroclaw Medical University, Wroclaw, Poland.
Genetics Department, Wroclaw Medical University, Wroclaw, Poland.
Pathol Res Pract. 2014 Dec;210(12):893-6. doi: 10.1016/j.prp.2014.07.010. Epub 2014 Aug 9.
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.
在不同细胞途径中发挥作用的蛋白酪氨酸磷酸酶，通常被描述为肿瘤抑制因子，但也有作为癌基因的情况。它们的作用此前已在结直肠癌以及胃癌、乳腺癌、甲状腺癌、前列腺癌、卵巢癌、胰腺癌、神经胶质瘤、肝癌、白血病和许多其他癌症中有所描述。在先前的一项研究中，我们描述了蛋白酪氨酸磷酸酶受体T型、M型、Z1型和Q基因（PTPRT、PTPRM、PTPRZ1和PTPRQ）在散发性结直肠癌中发生了高甲基化。因此，在本研究中，我们研究了覆盖这四个蛋白酪氨酸磷酸酶基因区域内的染色体不平衡改变与这种癌症的关系。对102个癌组织进行了分子特征分析，包括BRAF和K-ras突变分析以及甲基化表型分析。使用比较基因组杂交技术进行染色体畸变分析。我们观察到三个包含蛋白酪氨酸磷酸酶编码基因的区域发生了扩增，如PTPRZ1（7q31.3，23.5%的病例中扩增）、PTPRQ（12q21.2，5.9%的病例中扩增）、PTPRT（20q12，29.4%的病例中扩增），同时PTPRM区域（18p11.2）出现缺失（21.6%的病例中缺失）。这些数据可能表明，在散发性结直肠癌中，PTPRZ1、PTPRT、PTPRQ可能作为癌基因起作用，而PTPRM作为肿瘤抑制基因起作用。我们的研究还表明，20号染色体q12区域的增加和18号染色体p11.2区域的缺失与BRAF突变的缺失以及传统腺癌途径有关。
