Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The developmentally regulated HMGIC gene, which encodes an architectural transcription factor, has recently been linked to the pathogenesis of benign solid tumors with chromosome aberrations involving 12q13-15. Among these tumors are pleomorphic adenoma of the salivary glands, lipoma, uterine leiomyoma, hamartomas of the breast and lung, fibroadenoma of the breast, angiomyxoma, and endometrial polyps. For most tumor types, however, the translocation partners are variable. At present, no translocation partner genes of HMGIC are known for pleomorphic adenomas. Here, we report that in a primary pleomorphic adenoma of the parotid gland, the FHIT gene, which spans the chromosome 3p14.2 fragile site FRA3B, and is frequently disrupted in tumors, acts as a fusion partner of HMGIC. In addition to normal HMGIC and FHIT transcripts, an HMGIC/FHIT hybrid transcript as well as its reciprocal counterpart, FHIT/HMGIC, were found to be expressed by reverse transcription-PCR. The results establish the concurrent disruption of two tumor-associated genes in a benign tumor.
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PMID:Expression of reciprocal hybrid transcripts of HMGIC and FHIT in a pleomorphic adenoma of the parotid gland. 898 31

The translocation t(3;8)(p21;q12) is the most common chromosome abnormality observed in pleomorphic adenomas of the salivary glands. In this paper we describe the physical mapping of the breakpoints in an adenoma with a variant t(3;8), viz., an ins(8;3)(q12;p21.3p14.1). Using sequence-tagged sites (STSs) corresponding to landmarks within a previously identified yeast artificial chromosome (YAC) spanning the breakpoint in adenomas with t(3;8), cosmids isolated from a chromosome 8-specific cosmid library. The 8q12 insertion breakpoint was mapped by FISH to a 300-kb region flanked by MOS and a new STS, CH129. A cosmid within this region was shown to span the breakpoint. To test whether the recently identified FHIT gene, which maps to 3p14.2, was disrupted by the 3p rearrangement, we also isolated an FHIT YAC and mapped this YAC by FISH distal to the most proximal 3p breakpoint. In addition, RT-PCR analysis revealed only a normal-sized FHIT transcript, suggesting that FHIT is not affected by the 3;8-rearrangement.
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PMID:Mapping of the 8q12 translocation breakpoint to a 40-kb region in a pleomorphic adenoma with an ins(8;3)(q12;p21.3p14.1). 915 18

In the present study, we examined the status of the FHIT gene in 112 colorectal cancer and 137 colorectal adenoma specimens. In a total of 5 specimens (4 colorectal cancers and 1 colorectal adenoma), a common smaller product was detected in addition to the normal size product. This smaller product had lost exon 4, the 5' noncoding region of the FHIT gene, owing to alternative splicing. Moreover, all of the 5 tumors with alternative splicing were located lower on the rectum than the anterior peritoneal reflection.
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PMID:Alternative splicing of the FHIT gene in colorectal cancers. 919 30

It is unclear how expression of the FHIT (fragile histidine triad) gene by the colorectal neoplasm correlates with histogenesis and progression of the disease. We studied the association between expression of Fhit protein and development of colorectal carcinoma (CRC). We also examined relations between Fhit protein expression, macroscopic type, Ki-67 labeling index (LI), and p53 overexpression in carcinoma in situ. We examined 27 colorectal adenomas, 82 carcinomas in situ and 21 invasive CRCs resected endoscopically or surgically. The carcinomas in situ comprised three macroscopic types: polypoid (n=27), superficial (flat elevated, n=27; depressed, n=10) and granulonodular laterally spreading tumor (G-LST, n=23). Fhit, Ki-67, and p53 overexpression were examined immunohistochemically. Levels of Fhit protein were lower in invasive CRC than in adenoma and carcinoma in situ (p<0.01). In carcinoma in situ, reduced Fhit expression was observed in 7 of 22 (31.8%) polypoid types, 13 of 27 (48.1%) superficial flat elevated types, 8 of 10 (80%) superficial depressed types and 7 of 23 (30.4%) G-LST. Frequencies of reduced Fhit expression were significantly higher in the polypoid type and G-LST lesions than in the depressed type (p<0.05). Reduced expression of Fhit protein was related significantly to Ki-67 LI and p53 overexpression in carcinoma in situ (p<0.01). The present findings suggest that reduced expression of Fhit protein is related to development of colorectal neoplasm. Polypoid CRC and G-LST appear to differ from superficial depressed CRC in terms of Fhit expression.
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PMID:Clinical significance of Fhit expression in development of colorectal carcinoma of various macroscopic types. 1296 15

Serrated adenoma is a recently described entity characterized by having combined architectural features of hyperplastic polyps and classical adenoma. To understand the role of gene regulation in the progression of the serrated neoplasia pathway, we examined the methylation profiles of the promoter regions of 19 genes, DNA ploidy, and mutator phenotype status. In all, 40 sporadic, classical serrated adenomas were pathologically reviewed and divided into four pathologic groups according to their histologic grades. Methylation-specific PCR was performed using primers for p16, hMLH1, RASSF1A, APC, HIC-1, DAPK, MGMT, SLC5A8, RB1, H-Cadherin, E-Cadherin, TIMP3, PTEN, THBS1, LKB1, p14, p15, FHIT, and VHL. Dual flow-cytometric analyses using cytokeratin and DAPI and MSI studies using BAT26 were also performed. Methylation was observed in 2.5-82.5% (mean 33.9%) of the CpG islands in the promoter regions of 16 genes. The tumors with higher histologic grades, including carcinomas, showed more extensive methylation compared to those with lower grades, and serrated adenomas in the right colon showed more frequent methylation than those in the left (P<0.05). Tumor-specific promoter methylation of SLC5A8 was observed in 33 (82.5%) of the serrated adenomas. Aneuploidization with near-diploid DNA indices was detected in four out of 28 cases examined (14.3%); two were low-grade serrated adenomas and two were carcinomas in the left colon. The high mutator phenotype was not observed in any of the cases examined. Our results indicate that: (1) aberrant, widespread methylation of CpG islands increases with the histological progression of serrated adenomas; (2) methylation of SLC5A8 is an early event; and (3) additional methylation of the p16, p14, MGMT, TIMP3, and FHIT genes are important tumorigenic steps in the serrated neoplasia pathway.
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PMID:Progressive methylation during the serrated neoplasia pathway of the colorectum. 1538 52

Pancreatic mucinous cystic tumors (MCT) are proliferations of mucin-producing epithelia supported by an ovarian-like stroma. They are classified into adenomas (MCA), borderline (MCB) and noninvasive or invasive carcinomas (MCC). The molecular mechanisms underlying their clinical behavior are poorly understood, partly due to the lack of cellular models. We report the establishment of MCC1, the first cell line from a pancreatic MCT, deriving from the highly dysplastic cell component of a noninvasive MCC. MCC1 has mutations in codon 12 of K-RAS (GGT>GAT), codon 58 of P16 (CGA>TGA) and codon 132 of P53 (AAG>AGG). The FHIT and DPC4 genes are unaltered. Immunohistochemistry shows abnormal expression of MUC1 and p53, loss of p16 and retention of Fhit and Dpc4 in both the cell line and the highly dysplastic cells of the primary lesion. The morphological and molecular features of MCC1 and its corresponding primary tumor are consistent with a model for non-invasive MCC, where K-RAS, P16, P53 and MUC1 alterations are pre-invasive changes associated with progression of malignancy of MCT from adenoma to carcinoma. MCC1 is sensitive to 5-fluorouracil, representing the first assessment of drug sensitivity for MCC. Finally, MCC1 is a suitable model for preclinical studies, as it grows in immunodeficient mice.
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PMID:Mucinous cystic carcinoma of the pancreas: a unique cell line and xenograft model of a preinvasive lesion. 1568 69

To clarify the roles of FHIT (fragile histidine triad) and PTEN (phosphatase and tensin homology deleted from human chromosome 10) expression in the genesis and progression of gastric cancers, we examined expression of FHIT and PTEN on tissue microarray containing gastric normal mucosa (n=49), adenoma (n=49), noncancerous mucosa adjacent to carcinoma (n=84) and carcinoma (n=249) by immunohistochemistry. Their expression was compared with clinicopathologic parameters of tumors, including expression of p53 and cysteine protease protein 32 as well as survival time of patients with carcinoma. The results showed expression of FHIT and PTEN were lower in gastric carcinoma than those in normal mucosa, noncancerous mucosa adjacent to carcinoma and adenoma of the stomach (P<0.05). FHIT and PTEN expression showed a significantly negative association with depth of invasion, lymphatic invasion, and lymph node metastasis, liver metastasis, and Union Internationale Contre le Cancer staging of gastric carcinoma (P<0.05). Intestinal-type gastric carcinomas highly expressed FHIT and PTEN protein, compared with diffuse-type ones (P<0.05). Expression of FHIT and PTEN were positively related with expression of p53 and cysteine protease protein 32 in gastric carcinoma (P<0.05), as well as favorable prognosis of the patients with the tumors (P<0.05). There was positive relationship between FHIT and PTEN expression in gastric carcinoma (P<0.05). It was suggested that down-regulated expression of FHIT and PTEN contributed to gastric carcinogenesis possibly by involving in the imbalance between apoptosis and proliferation of cells. Their altered expression underlay the molecular basis of invasion, metastasis, differentiation of gastric carcinoma.
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PMID:Low expression of FHIT and PTEN correlates with malignancy of gastric carcinomas: tissue-array findings. 1809 87

Appendiceal mucinous neoplasms have been the focus of considerable debate in recent years. We histologically classified 70 appendiceal mucinous neoplasms into three categories: 32 mucinous adenoma, 23 mucinous neoplasm of uncertain malignant potential, and 15 mucinous adenocarcinomas. Immunohistochemistry was performed for 24 proteins in different functional categories, specifically, oncogenic proteins (bcl-2, beta-catenin, CEA, C-erbB2, c-kit, Cox-2, Cyclin D1, EGFR, Ki-67, NF-kappaB, VEGF), tumor suppressors (E-cadherin, FHIT, hMLH1, p53, p63, smad4), cell-cycle regulators (p21, p27, p16), and mucin proteins (MUC1, MUC2, MUC5AC, MUC6). Our data showed that 9 out of the 24 proteins were more frequently altered in the mucinous adenocarcinoma group than in the mucinous adenoma group (P<0.05), including beta-catenin (13% in mucinous adenoma vs 60% in mucinous adenocarcinoma), CyclinD1 (44 vs 87%), Ki-67 (high labeling index: 31 vs 67%), NF-kappaB (19 vs 60%), VEGF (16 vs 87%), E-cadherin (0 vs 47%), p53 (6 vs 40%), MUC2 (9 vs 67%), and MUC5AC (3 vs 40%). The distinct immunoexpression profile of mucinous neoplasm of uncertain malignant potential was placed between those of mucinous adenoma and mucinous adenocarcinoma (P<0.05). Moreover, the mucinous adenoma, mucinous neoplasm of uncertain malignant potential, and mucinous adenocarcinoma categories displayed differences in terms of the number of altered markers among the nine proteins (P<0.05; mean 1.4 vs 2.6 vs 5.5, respectively). In mucinous adenocarcinoma, the p53 status was related to disease-free survival and overall survival of patients (P<0.05, both). NF-kappaB status and the number of altered protein markers made statistically marginal impacts on disease-free survival; also beta-catenin loss, on overall survival of patients. In conclusion, protein immunoexpression profiles may facilitate the classification of appendiceal mucinous neoplasms. In our study, the three tumor categories of mucinous adenoma, mucinous neoplasm of uncertain malignant potential, and mucinous adenocarcinoma exhibited distinct immunoexpression profiles. Five and more altered protein markers, p53 overexpression, NF-kappaB positivity, and beta-catenin loss were predictive factors of adverse clinical outcomes in appendiceal mucinous adenocarcinomas.
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PMID:Differential protein immunoexpression profiles in appendiceal mucinous neoplasms: a special reference to classification and predictive factors. 1944 92

The morphologic distinction of pleomorphic adenoma from other benign or low-grade salivary gland tumors is sometimes difficult and problematic because of their potentially overlapping histological patterns. A subset of pleomorphic adenoma harbors specific gene alterations involving PLAG1 or HMGA2, and the detection of these fusion genes and their products using formalin-fixed, paraffin-embedded (FFPE) tumor specimens may be a useful diagnostic adjunct. In the present study, gene fusions involving PLAG1 or HMGA2 were examined by reverse transcription-polymerase chain reaction (RT-PCR) analysis, with FFPE tumor tissues and immunohistochemical expression of PLAG1 in 45 pleomorphic adenomas, using a commercially available antibody. RT-PCR analyses identified the CTNNB1-PLAG1, LIFR-PLAG1, CHCHD7-PLAG1, and HMGA2-WIF1 fusion transcripts in eight, two, one, and one case, respectively. The TCEA1-PLAG1, HMGA2-FHIT, and HMGA2-NFIB fusion transcripts were not detected. Immunohistochemically, tumor cells in all 45 pleomorphic adenomas were positive for PLAG1, irrespective of PLAG1 rearrangements, even in the case with the HMGA2-WIF1 fusion transcript. Tumor cells displaying myoepithelial or cartilaginous differentiation were almost constantly positive for PLAG1, whereas a limited expression was observed in glandular or keratinizing cells. Among the 46 tumors other than pleomorphic adenoma, 4 carcinomatous components of carcinomas ex pleomorphic adenoma were positive for PLAG1, the other 39 were negative for PLAG1, and the remaining 3 were only faintly and/or focally stained, indicating that the immunohistochemical detection of PLAG1 is diagnostically useful. The present results also suggest that overexpression of PLAG1 is essential for the tumorigenesis of pleomorphic adenomas, although the mechanisms mediating PLAG1 overexpression seem to be variable.
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PMID:Aberrant PLAG1 expression in pleomorphic adenomas of the salivary gland: a molecular genetic and immunohistochemical study. 2139 49

Cutaneous mixed tumors, also known as chondroid syringomas, are benign cutaneous adnexal tumors that exhibit remarkable histopathological similarities to pleomorphic adenoma of the salivary gland. Thus far, there is little information on the genetic profiles of cutaneous mixed tumors, although specific genetic aberrations including fusion genes involving PLAG1 and HMGA2 have been demonstrated in pleomorphic adenomas. In the present study, we conducted an immunohistochemical evaluation of PLAG1 and a reverse transcription-polymerase chain reaction (RT-PCR) assay to detect fusion gene transcripts associated with pleomorphic adenoma, including the CTNNB1-PLAG1, LIFR-PLAG1, CHCHD7-PLAG1, TCEA1-PLAG1, HMGA2-FHIT, HMGA2-NFIB, and HMGA2-WIF1 fusion transcripts; this was performed using formalin-fixed paraffin-embedded tumor tissue specimens of 16 cutaneous mixed tumors including one sample with an adenocarcinoma component. All 16 cutaneous mixed tumors were immunoreactive to PLAG1, which was predominantly expressed in cells with myoepithelial or chondroid differentiation accounting for >80% of cells, whereas PLAG1 expression in glandular or squamous tumor cells was restricted to <20% of cells. The carcinoma component in the mixed tumor was also positive for PLAG1. On the other hand, all eight cutaneous adnexal tumors other than the mixed tumor were negative for PLAG1. In RT-PCR analysis, no fusion gene transcripts involving PLAG1 or HMGA2 were identified in any of the cases. Concordant with previous studies, our results support the close relationship between cutaneous mixed tumors and pleomorphic adenomas of the salivary gland. However, the mechanism of PLAG1 expression in cutaneous mixed tumors appears to be possibly different from that of pleomorphic adenomas.
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PMID:PLAG1 expression in cutaneous mixed tumors: an immunohistochemical and molecular genetic study. 2192 43


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