Topographic Molecular Profile of Pheochromocytomas: Role of Somatic Down-Regulation of Mismatch Repair

Blanes, Alfredo; Sanchez-Carrillo, Juan J.; Díaz‐Cano, Salvador

doi:10.1210/jc.2005-1645

Cited by 22 publications

(60 citation statements)

References 43 publications

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“…DNA was extracted from the most cellular areas of junctional, superficial, and deep compartments, 17,20,23,24 after microdissecting at least 100 cells (B0.4 mm 2 , PixCell II Laser Capture Microdissection, Arcturus Engineering Inc., Mountain View, CA, USA) from two 20-mm unstained paraffin sections/compartment (Figure 1). Appropriate controls (histologically normal epidermis and dermis) and quality assurance (sensitivity, specificity, positive and negative) were run for each test.…”

Section: Tsg Microsatellite Analysismentioning

confidence: 99%

“…26 DNA was then used for polymerase chain reaction (PCR) amplification of the intron microsatellites of tumor suppressor genes (Table 2). 17,20 Multiplex PCR was performed using Qiagen s multiplex PCR kit (Qiagen Ltd., West Sussex, UK). Each multiplex PCR reaction included 5 ml Qiagen multiplex PCR master mix, 1 ml of 10 Â primer mix, 2 ml distilled water, and 2 ml genomic DNA.…”

Section: Tsg Microsatellite Analysismentioning

confidence: 99%

“…7,18,20,24,27,28 This ratio represents 80% of clonal cells in the sample and hence was used to increase the detection specificity. 7 (b) Additional allele bands present in tumor samples but not in the corresponding controls were considered as evidence of somatic microsatellite abnormalities.…”

Section: Tsg Microsatellite Analysismentioning

confidence: 99%

“…7 (b) Additional allele bands present in tumor samples but not in the corresponding controls were considered as evidence of somatic microsatellite abnormalities. 7,19,20,29 Immunohistochemical Detection of Ki-67, Cell Cycle Regulators, and TERT Sections were mounted on positively charged slides (Superfrost Plus, Fisher Scientific, Fair Lawn, NJ, USA), baked at 601C for 2 h, and processed as described. 22,24,30 After routine dewaxing and rehydration, endogenous peroxidase quenching, and antigen heat retrieval, the slides were transferred to a moist chamber.…”

Section: Tsg Microsatellite Analysismentioning

confidence: 99%

“…19,20 However, the association of multiple genetic alterations would become statistically less probable as the number of molecular markers increases and is useful to test clonal expansions in tumors. 7,18 Although genetic abnormalities are probably asymmetrically acquired, there is a correlation with tumor cell topography in both luminal and solid organs, 1,[19][20][21][22][23] which has not been assessed in skin melanocytic lesions. Any potential topographic segregation of tumor cells will influence interpretations of the results, supporting a linear model if progressive grading is parallel to intraepithelial-to-invasive topography of tumor cells.…”

mentioning

confidence: 99%

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Heterogeneous topographic profiles of kinetic and cell cycle regulator microsatellites in atypical (dysplastic) melanocytic nevi

et al. 2011

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Atypical (dysplastic) melanocytic nevi are clinically heterogeneous malignant melanoma precursors, for which no topographic analysis of cell kinetic, cell cycle regulators and microsatellite profile is available. We selected low-grade atypical melanocytic nevi (92), high-grade atypical melanocytic nevi (41), melanocytic nevi (18 junctional, 25 compound) and malignant melanomas (16 radial growth phase and 27 vertical growth phase). TP53, CDKN2A, CDKN1A, and CDKN1B microsatellite patterns were topographically studied after microdissection; Ki-67, TP53, CDKN2A, CDKN1A, and CDKN1B expressions and DNA fragmentation by in situ end labeling for apoptosis were topographically scored. Results were statistically analyzed. A decreasing junctional-dermal marker expression gradient was observed, directly correlating with atypical melanocytic nevus grading. High-grade atypical melanocytic nevi revealed coexistent TP53-CDKN2A-CDKN1B microsatellite abnormalities, and significantly higher junctional Ki67-TP53 expression (inversely correlated with CDKN1A-CDKN1B expression and in situ end labeling). Malignant melanomas showed coexistent microsatellite abnormalities (CDKN2A-CDKN1B), no topographic gradient, and significantly decreased expression. Melanocytic nevi and low-grade atypical melanocytic nevi revealed sporadic junctional CDKN2A microsatellite abnormalities and no significant topographic kinetic differences. High-grade atypical melanocytic nevi accumulate junctional TP53-CDKN1A-CDKN1B microsatellite abnormalities, being progression TP53-independent and better assessed in the dermis. Melanocytic nevi and low-grade atypical melanocytic nevi show low incidence of microsatellite abnormalities, and kinetic features that make progression unlikely.

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Section: Tsg Microsatellite Analysismentioning

confidence: 99%

Section: Tsg Microsatellite Analysismentioning

confidence: 99%

Section: Tsg Microsatellite Analysismentioning

confidence: 99%

Section: Tsg Microsatellite Analysismentioning

confidence: 99%

mentioning

confidence: 99%

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Heterogeneous topographic profiles of kinetic and cell cycle regulator microsatellites in atypical (dysplastic) melanocytic nevi

et al. 2011

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Metastasis‐associated gene expression profile of liver and subcutaneous lesions derived from mouse pheochromocytoma cells

Lai

Morris

Pang

et al. 2007

Molecular Carcinogenesis

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The development of metastatic cancer is associated with overexpression or downregulation of specific genes and cell regulatory pathways. Some of these genes and pathways may be involved in invasion and dissemination of tumor cells, while others may promote seeding, survival or growth of cells at specific distant sites. In this investigation, gene expression profiles of nonmetastasizing tumors generated by injecting mouse pheochromocytoma cells (MPCs) subcutaneously were compared to those of liver tumors generated by injecting the cells intravenously. Both were compared to the cultured parental cell line. Tumors in the liver have a route of spread, anatomical distribution, and growth environment similar to naturally metastasizing pheochromocytomas, while intravenous injection of cells bypasses the initial steps of metastasis occurring spontaneously from a primary tumor. Eight genes were upregulated in liver tumors, 15 in subcutaneous tumors and seven in both compared to the cultured cells. Using quantitative real-time PCR, expression of five genes (Metap2, Reck, S100a4, Timp2, and Timp3) was verified as significantly lower in liver tumors than in subcutaneous tumors. Downregulation of these genes has been previously been associated with malignancy of pheochromocytomas. These findings indicate that different microenvironments can differentially affect the expression of metastasis-related genes in pheochromocytomas, and that overexpression or underexpression of these genes need not be present when the tumor cells are initially disseminated. The hepatic localization of tumors formed by intravenously injected MPC cells and the tumors' gene expression profile resembling that of naturally occurring pheochromocytoma metastases support the use of this model to study pheochromocytoma metastasis.

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Differential proteomic analysis of adrenal gland during postnatal development

2009

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The adrenal glands (AGs) are endocrine organs essential for life. They undergo a fetal to adult developmental maturation process, occurring in rats during the first postnatal month. The molecular modifications underlying these ontogenic changes are essentially unknown. Here we report the results of a comparative proteomic analysis performed on neonatal (Postnatal day 3) versus adult (Postnatal day 30) AGs, searching for proteins with a relative higher abundance at each age. We have identified a subset of proteins with relevant expression in each developmental period using 2-DE and DIGE analysis. The identified proteins belong to several functional categories, including proliferation/differentiation, cell metabolism, and steroid biosynthesis. To study if the changes in the proteome are correlated with changes at the mRNA level, we have randomly selected several proteins with differential expression and measured their relative mRNA levels using quantitative RT-PCR. Cell-cycle regulating proteins (retinoblastoma binding protein 9 and prohibitin) with contrasting effects on proliferation are expressed differentially in neonatal and adult AG. Progesterone metabolizing enzymes, up-regulated in the neonatal gland, might contribute to the hyporesponsiveness of the adrenal cortex characteristic of this developmental period. We have also observed in the adult gland a marked up-regulation of enzymes involved in NAD(P)H production, thus providing the reducing power necessary for steroid hormone biosynthesis.

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Topographic Molecular Profile of Pheochromocytomas: Role of Somatic Down-Regulation of Mismatch Repair

Cited by 22 publications

References 43 publications

Heterogeneous topographic profiles of kinetic and cell cycle regulator microsatellites in atypical (dysplastic) melanocytic nevi

Heterogeneous topographic profiles of kinetic and cell cycle regulator microsatellites in atypical (dysplastic) melanocytic nevi

Metastasis‐associated gene expression profile of liver and subcutaneous lesions derived from mouse pheochromocytoma cells

Differential proteomic analysis of adrenal gland during postnatal development

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