Abstract | BACKGROUND: The PML gene is fused to the RARalpha gene in the vast majority of acute promyelocytic leukemias (APL) and has been implicated in the control of key tumor-suppressive pathways. However, its role in the pathogenesis of human cancers other than APL is still unclear. We therefore assessed the status and expression of the PML gene in solid tumors of multiple histologic origins. METHODS: We created tumor tissue microarrays ( TTMs) with samples from patients with colon adenocarcinoma (n = 109), lung carcinoma (n = 19), prostate adenocarcinoma (n = 36), breast carcinoma (n = 38), central nervous system (CNS) tumors (n = 51), germ cell tumors (n = 60), thyroid carcinoma (n = 32), adrenal cortical carcinoma (n = 12), and non-Hodgkin's lymphoma (n = 251) and from normal tissue corresponding to each histotype and analyzed PML protein and mRNA expression by immunohistochemistry and in situ hybridization, respectively. Tumor cell lines (n = 64) of various histologic origins were analyzed for PML protein and mRNA expression by immunofluorescence and northern blotting, respectively. DNA from microdissected tumor samples and cell lines was analyzed for PML mutations and loss of heterozygosity (LOH). For some tumor types, the association between PML expression and tumor stage and grade was analyzed. Statistical tests were two-sided. RESULTS: CONCLUSIONS: PML protein expression is frequently lost in human cancers of various histologic origins, and its loss associates with tumor grade and progression in some tumor histotypes.
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Authors | Carmela Gurrieri, Paola Capodieci, Rosa Bernardi, Pier Paolo Scaglioni, Khedoudja Nafa, Laura J Rush, David A Verbel, Carlos Cordon-Cardo, Pier Paolo Pandolfi |
Journal | Journal of the National Cancer Institute
(J Natl Cancer Inst)
Vol. 96
Issue 4
Pg. 269-79
(Feb 18 2004)
ISSN: 1460-2105 [Electronic] United States |
PMID | 14970276
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- DNA Primers
- Neoplasm Proteins
- Nuclear Proteins
- Promyelocytic Leukemia Protein
- RARA protein, human
- RNA, Messenger
- Receptors, Retinoic Acid
- Retinoic Acid Receptor alpha
- Transcription Factors
- Tumor Suppressor Proteins
- PML protein, human
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Topics |
- Adenocarcinoma
(genetics)
- Adrenal Cortex Neoplasms
(genetics)
- Blotting, Northern
- Breast Neoplasms
(genetics)
- Carcinoma
(genetics, pathology)
- Central Nervous System Neoplasms
(genetics)
- Colonic Neoplasms
(genetics)
- DNA Primers
- Female
- Fluorescent Antibody Technique
- Gene Expression Regulation, Neoplastic
- Germinoma
(genetics)
- Humans
- Loss of Heterozygosity
- Lung Neoplasms
(genetics)
- Male
- Mutation
- Neoplasm Proteins
(genetics)
- Neoplasm Staging
- Nuclear Proteins
- Polymerase Chain Reaction
- Promyelocytic Leukemia Protein
- Prostatic Neoplasms
(genetics)
- Protein Array Analysis
- RNA, Messenger
(metabolism)
- Receptors, Retinoic Acid
(genetics)
- Retinoic Acid Receptor alpha
- Thyroid Neoplasms
(genetics)
- Transcription Factors
(genetics)
- Tumor Suppressor Proteins
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