Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have suggested the involvement of tumour-suppressor genes on chromosomes 8p, 22q and 18q (DCC) in prostate cancer. The aim of this study was to further characterize these regions. We investigated 20 polymorphic regions on the 3 chromosome arms in 43 cancers and 10 cases of benign prostatic hyperplasia (BPH). Allelic loss was observed in 72% of cancers on 8p, 16% on 22q and 24% at DCC. For BPH, loss was observed in 20% on 8p and in 12% at DCC. The low incidence of LOH on 22q implies that this locus has no significant role in prostate carcinogenesis. At DCC, although the overall incidence was low, tumours with LOH were mostly of high grade or had metastases, suggesting a role for this gene in prostate cancer progression. On chromosome 8p, 29% of cancers had deletions at the LPL locus on 8p22 and 60% had deletions within a region flanked by the markers D8S339 and ANKI on 8p 11.1-p21.1. Within this region, 2 distinct areas of allelic loss were observed, at one or both ANKI and D8S255, and in the region defined by the markers D8S259-D8S505. For the regions 8p22 and ANKI-D8S255, tumours with metastases had a greater frequency of LOH compared to non-metastasizing tumours, suggesting the presence of putative metastasis-suppressor genes in these regions.
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PMID:Allelic loss on chromosomes 8p, 22q and 18q (DCC) in human prostate cancer. 879 71

Loss of heterozygosity at chromosome 8p21-22 is common in human prostate cancer, suggesting the presence of one or more tumor suppressor genes at this locus. A homeobox gene that is expressed specifically in adult human prostate, NKX3.1, the expression of which is regulated by androgen, maps to chromosome 8p21. Fine structure in situ mapping showed that NKX3.1 is proximal to MSR32 (macrophage scavenger receptor type II) and LPL (human lipoprotein lipase) and very close to NEFL (human neurofilament light chain) on 8p21. Single-strand conformational polymorphism analysis of 48 radical prostatectomy cancer specimens and 3 metastases for the entire coding region of NKX3.1 showed no tumor-specific sequence alterations in 50 specimens and total absence of the gene in 1 specimen known to have a biallelic deletion of 8p21. NKX3.1 was found to have a polymorphism at nucleotide 154 in codon 52 that resulted in a CGC-->TGC sequence change and an Arg-->Cys amino acid alteration (R52C). This polymorphism was present in 20% of DNA samples. If NKX3.1 is a target of the 8p21 LOH, it is not via disruption of the coding region of the gene.
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PMID:Coding region of NKX3.1, a prostate-specific homeobox gene on 8p21, is not mutated in human prostate cancers. 937 51

To determine whether genetic changes are markers of cancer progression and patient survival in Stage T(2-3)N(1-3)M(0) prostatic carcinoma, we compared 26 patients who died of tumor relapse after prostatectomy and lymphadenectomy (case group) with 26 matched patients who were alive at the time of the matched case's death (control group). Nine unmatched cases were also included in this study. In 37 cases, paired primary tumors (119 foci) and lymph node metastases (114 foci) were available for study. Fluorescence in situ hybridization (FISH) with centromere-specific probes for chromosomes 7, 8, and 17 and region-specific probes for D7S486 (7q31), c-myc (8q24), LPL (8p22), and p53 (17p13) was performed on available primary carcinomas and lymph node metastases. In primary tumor foci, +7q31, -8p22, +c-myc, substantial additional increases of myc (AI-c-myc), and -p53 were observed in 65%, 74%, 43%, 29%, and 31% of foci, respectively. AI-c-myc was strongly associated with higher cancer Gleason score (P =.003). Heterogeneity of genetic changes was frequently observed among multiple cancer foci. Lymph node metastases of prostate cancer usually shared genetic changes with paired primary tumors. In addition, the genetic change pattern with -8p, +c-myc or AI-c-myc, +7q, and +p53 was slightly higher in lymph node metastases (22%) than in primary tumors (6%) (P =.08). In matched case and control patients, simultaneous gain of 7q31 (+7q31) and CEP7 (+CEP7) was identified in 59% and 68% of specimens for case and control groups, respectively (P =.48). Loss of 8p22 (-8p22) was identified in 77% and 69% of specimens for case and control groups, respectively (P = 1.0). Simultaneous gain of c-myc (+c-myc) and CEP8 (+CEP8) without overt additional increase of c-myc copy number relative to CEP8 copy number, was identified in 38% and 54% of specimens for case and control groups, respectively (P =.27). AI-c-myc was identified in 54% and 23% of specimens for case and control groups, respectively (odds ratio = 3.0, P =.06). Loss of p53 (-p53) was identified in 46% and 15% of specimens for case and control groups, respectively (odds ratio = 4.0, P =.04). Our results indicate that FISH anomalies are very common in both primary tumors and lymph node metastases of Stage T(2-3)N(1-3)M(0) prostate cancer; that AI-c-myc is associated with higher cancer Gleason score; that AI-c-myc and -p53 are associated with prostate cancer progression and are potential markers of survival in Stage T(2-3)N(1-3)M(0) prostate cancer; and that lymph node metastases usually have similar or additional genetic changes compared with primary tumors, and multiple lymph node metastases usually have similar genetic changes.
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PMID:Loss of p53 and c-myc overrepresentation in stage T(2-3)N(1-3)M(0) prostate cancer are potential markers for cancer progression. 1179 39

Oral squamous cell carcinoma (OSCC) is a common worldwide malignancy. However, it is unclear what, if any, genomic alterations occur as the disease progresses to invasive and metastatic OSCC. This study used genomewide array-CGH in microdissected specimens to map genetic alterations found in primary OSCC and neck lymph node metastases. We used array-based comparative genomic hybridization (array-CGH) to screen genomewide alterations in eight pairs of microdissected tissue samples from primary and metastatic OSCC. In addition, 25 primary and metastatic OSCC tissue pairs were examined with immunohistochemistry for protein expression of the most frequently altered genes. The highest frequencies of gains were detected in LMYC, REL, TERC, PIK3CA, MYB, MDR1, HRAS, GARP, CCND2, FES, HER2, SIS, and SRY. The highest frequencies of losses were detected in p44S10, TIF1, LPL, MTAP, BMI1, EGR2, and MAP2K5. Genomic alterations in TGFbeta2, cellular retinoid-binding protein 1 gene (CRBP1), PIK3CA, HTR1B, HRAS, ERBB3, and STK6 differed significantly between primary OSCC and their metastatic counterparts. Genomic alterations in PRKCZ, ABL1, and FGF4 were significantly different in patients who died compared with those who survived. Immunohistochemistry confirmed high PIK3CA immunoreactivity in primary and metastatic OSCC. Higher FGF4 immunoreactivity in primary OSCC is associated with a worse prognosis. Loss of CRBP1 immunoreactivity is evident in primary and metastatic OSCC. Our study suggests that precise genomic profiling can be useful in determining gene number changes in OSCC. As our understanding of these changes grow, this profiling may become a practical tool for clinical evaluation.
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PMID:Array-comparative genomic hybridization to detect genomewide changes in microdissected primary and metastatic oral squamous cell carcinomas. 1667 65