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Target Concepts:
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Query: EC:2.7.10.1 (
ERK
)
95,504
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Chromosomal rearrangements of the RET proto-oncogene (
RET
/PTC) are the common feature of papillary thyroid carcinoma (PTC). In this study, we report the identification, cloning, and functional characterization of a novel type of
RET
/PTC rearrangement that results from the fusion of the 3'-portion of
RET
coding for the tyrosine kinase (TK) domain of the receptor to the 5'-portion of the Homo sapiens
hook homolog 3
(
HOOK3
) gene. The novel fusion was identified in a case of PTC that revealed a gene expression signature characteristic of
RET
/PTC on DNA microarray analysis, but was negative for the most common types of
RET
rearrangement. A fusion product between exon 11 of
HOOK3
and exon 12 of
RET
gene was identified by 5'RACE, and the presence of chimeric
HOOK3
-RET protein of 88 kDa was detected by western blot analysis with an anti-
RET
antibody. The protein is predicted to contain a portion of the coiled-coil domains of
HOOK3
and the intact TK domain of
RET
. Expression of the
HOOK3
-
RET
cDNA in NIH3T3 cells resulted in the formation of transformed foci and in tumor formation after injection into nude mice, confirming the oncogenic nature of
HOOK3
-
RET
.
...
PMID:HOOK3-RET: a novel type of RET/PTC rearrangement in papillary thyroid carcinoma. 1763 57
Papillary thyroid carcinomas are the most common type of thyroid oncopathology, and are rather often associated with the expression of
RET
/PTC oncogens. The first oncogen
RET
/PTC1 was isolated more than 20 years ago. Now 13 different forms of
RET
/PTC are known, and 12 different partner-genes are described, that could be involved in formation of
RET
/PTC oncogenes. The most common of them are
RET
/PTC1 and
RET
/PTC3 forms. The great majority of oncogens
RET
/PTC, except for two--ELKS-
RET
and
HOOK3
-
RET
, have been founded in radioaction-induced thyroid tumors. There is an opinion that the key role in development of papillary thyroid carcinomas belongs to
RET
/PTC oncogens. The data about different types of
RET
/PTC oncogens, factors, that lead to their formation have been described in the present review. Also different mechanisms of activation of transduction pathways and gene's expression in thyroid cells after
RET
/PTC induction have been presented.
...
PMID:[Oncogenes RET/PTC and mechanisms of their involvement in thyroid cancerogenesis]. 2038 55
Prostate cancer, the most common male cancer in Western countries, is commonly detected with complex chromosomal rearrangements. Following the discovery of the recurrent TMPRSS2:ETS fusions in prostate cancer and EML4:
ALK
in non-small-cell lung cancer, it is now accepted that fusion genes not only are the hallmark of haematological malignancies and sarcomas, but also play an important role in epithelial cell carcinogenesis. However, previous studies aiming to identify fusion genes in prostate cancer were mainly focused on expression changes and fusion transcripts. To investigate the genes recurrently affected by the chromosome breakpoints in prostate cancer, we analysed Affymetrix array 6.0 and 500K SNP microarray data from 77 prostate cancer samples. While the two genes most frequently affected by genomic breakpoints were, as expected, ERG and TMPRSS2, surprisingly more known tumour suppressor genes (TSGs) than known oncogenes were identified at recurrent chromosome breakpoints. Certain well-characterised TSGs, including p53, PTEN, BRCA1 and BRCA2 are recurrently truncated as a result of chromosome rearrangements in prostate cancer. Interestingly, many of the genes residing at recurrent breakpoint sites have not yet been implicated in prostate carcinogenesis such as
HOOK3
, PPP2R2A and TCBA1. We have confirmed the generally reduced expression of selected genes in clinical samples using quantitative RT-PCR analysis. Subsequently, we further investigated the genes associated with the t(4:6) translocation in LNCaP cells and reveal the genomic fusion of SNX9 and putative TSG UNC5C, which led to the reduced expression of both genes. This study reveals another common mechanism that leads to the inactivation of TSGs in prostate cancer and the identification of multiple TSGs inactivated by chromosome rearrangements will lead to new direction of research for the molecular basis of prostate carcinogenesis.
...
PMID:Chromosome rearrangement associated inactivation of tumour suppressor genes in prostate cancer. 2199 1
Small intestine neuroendocrine tumors (SI-NETs) are the most common malignancy of the small bowel. Several clinical trials target PI3K/Akt/mTOR signaling; however, it is unknown whether these or other genes are genetically altered in these tumors. To address the underlying genetics, we analyzed 48 SI-NETs by massively parallel exome sequencing. We detected an average of 0.1 somatic single nucleotide variants (SNVs) per 106 nucleotides (range, 0-0.59), mostly transitions (C>T and A>G), which suggests that SI-NETs are stable cancers. 197 protein-altering somatic SNVs affected a preponderance of cancer genes, including
FGFR2
, MEN1,
HOOK3
, EZH2, MLF1, CARD11, VHL, NONO, and SMAD1. Integrative analysis of SNVs and somatic copy number variations identified recurrently altered mechanisms of carcinogenesis: chromatin remodeling, DNA damage, apoptosis, RAS signaling, and axon guidance. Candidate therapeutically relevant alterations were found in 35 patients, including SRC, SMAD family genes, AURKA,
EGFR
, HSP90, and
PDGFR
. Mutually exclusive amplification of AKT1 or AKT2 was the most common event in the 16 patients with alterations of PI3K/Akt/mTOR signaling. We conclude that sequencing-based analysis may provide provisional grouping of SI-NETs by therapeutic targets or deregulated pathways.
...
PMID:The genomic landscape of small intestine neuroendocrine tumors. 2367 60
Somatic copy number alterations (CNA) are common in endometrial serous carcinoma (ESC). We used the Tumor Cancer Genome Atlas Pan Cancer dataset (TCGA Pan Can) to explore the impact of somatic CNA and gene expression levels (mRNA) of cancer-related genes in ESC. Results were correlated with clinico-pathologic parameters such as age of onset, disease stage, progression-free survival (PFS) and overall survival (OS) (n = 108). 1,449 genes with recurrent somatic CNA were identified, observed in 10% or more tumor samples. Somatic CNA and mRNA expression levels were highly correlated (r> = 0.6) for 383 genes. Among these, 45 genes were classified in the Tier 1 category of Cancer Genome Census-Catalogue of Somatic Mutations in Cancer. Eighteen of 45 Tier 1 genes had highly correlated somatic CNA and mRNA expression levels including ARNT, PIK3CA, TBLXR1, ASXL1, EIF4A2,
HOOK3
, IKBKB, KAT6A, TCEA1, KAT6B,
ERBB2
, BRD4, KEAP1, PRKACA, DNM2, SMARCA4, AKT2, SS18L1. Our results are in agreement with previously reported somatic CNA for
ERBB2
, BRD4 and PIK3C in ESC. In addition, AKT2 (p = 0.002) and KAT6A (p = 0.015) amplifications were more frequent in tumor samples from younger patients (<60), and CEBPA (p = 0.028) and MYC (p = 0.023) amplifications were more common with advanced (stage III and IV) disease stage. Patients with tumors carrying KAT6A and MYC amplifications had shorter PFS and OS. The hazard ratio (HR) of KAT6A was 2.82 [95 CI 1.12-7.07] for PFS and 3.87 [95 CI 1.28-11.68] for OS. The HR of MYC was 2.25 [95 CI 1.05-4.81] and 2.62[95 CI 1.07-6.41] for PFS and OS, respectively.
...
PMID:KAT6A amplifications are associated with shorter progression-free survival and overall survival in patients with endometrial serous carcinoma. 3287 61
