Concurrent disruption of cell cycle associated genes in mantle cell lymphoma: a genotypic and phenotypic study of cyclin D1, p16, p15, p53 and pRb

Grønbæk, Kirsten; Nedergaard, Trine; Andersen, M. S.; Straten, Per thor; Guldberg, Per; Möller, Peter; Zeuthen, Jesper; Hansen, N. E.; Hou‐Jensen, Klaus; Ralfkiær, Elisabeth

doi:10.1038/sj.leu.2401090

Cited by 42 publications

(10 citation statements)

References 15 publications

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“…Staining was performed with a biotin–streptavidin method using biotinylated antimouse or antirabbit immunoglobulin followed by peroxidase‐conjugated streptavidin. 16 Peroxidase was developed using an H 2 O 2 /3‐amino‐9‐ethylcarbazole substrate (Dako ChemMate Detection Kit ® ). The specimens were counterstained with haematoxylin, mounted in Glycergel ® and examined by light microscopy.…”

Section: Methodsmentioning

confidence: 99%

Primary cutaneous B-cell lymphoma: a clinical, histological, phenotypic and genotypic study of 21 cases

Grønbæk

Möller

Nedergaard

et al. 2000

British Journal of Dermatology

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The clinical, histological, phenotypic and genotypic features of 21 primary cutaneous B-cell lymphomas (CBCLs) have been investigated. The patients were 13 men and eight women aged 34-91 years (median 67) at diagnosis. Eighteen patients had localized disease, and three had multiple skin lesions at diagnosis. Twelve patients developed cutaneous or extracutaneous recurrences, and five died from malignant lymphoma 7-84 months (median 36) after diagnosis. Histological examination showed features of marginal zone/mucosa-associated lymphoid tissue (MALT)-type lymphoma in 12 cases. Three of these had transformed to diffuse large B-cell lymphoma (DLBCL) in relapse biopsies. The remaining cases were seven primary DLBCLs and two cases tentatively classified as follicle centre cell (FCC) lymphoma. The neoplastic B cells showed similar phenotypes and genotypes in most cases (CD20+, CD79+, CD5-, CD10-, cyclin D1-, bcl-2+, bcl-x-, bax-, t(14;18)-negative). p53 protein was expressed in five cases, and four harboured mis-sense or loss-of-function mutations in the p53 gene. Deletion or promoter region hypermethylation of the p16INK4a gene was detected in two patients with DLBCL. The level of retinoblastoma protein expression and the proliferative fraction were significantly higher in DLBCL (> 50%) than in MALT- or FCC-type lymphomas (< 10%). Features associated with an unfavourable prognosis were the presence of multiple skin lesions at diagnosis, transformation from MALT-type lymphoma to DLBCL, and possibly p16INK4a aberrations. It is concluded that most CBCLs are dissimilar from FCC lymphomas and seem to be more closely related to marginal zone/MALT-type lymphomas. It is also suggested that there are fundamental differences between DLBCL and other histological categories of CBCL, indicating that cutaneous DLBCL is a separate entity with an increased growth potential and genetic features similar to DLBCL originating in other anatomical sites.

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Section: Methodsmentioning

confidence: 99%

Primary cutaneous B-cell lymphoma: a clinical, histological, phenotypic and genotypic study of 21 cases

Grønbæk

Möller

Nedergaard

et al. 2000

British Journal of Dermatology

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“…However, the molecular pathogenesis of gastric cancer is still unclear. There are accumulating evidences that human cancers including gastric cancer cells have escape mechanisms from death receptor-mediated apoptosis such as the mutations of primary structure of death receptors (Grùnbñk et al, 1998;Fisher et al, 1995;Landowsky et al, 1997;Lee et al, 1999;Shin et al, 1999;Park et al, 2001), the production of soluble Fas (Lee et al, 1998b), and ampli®cation of a decoy receptor (Pitti et al, 1998). In addition, chromsome 2q33, where the caspases-8 and -10 genes reside (Fernandes-Alnemri et al, 1996), has been reported as a commonly deleted region in gastric cancer (Nishizuka et al, 1998) and lung cancer (Otsuka et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Inactivating mutations of the caspase-10 gene in gastric cancer

et al. 2002

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We have analysed the genetic alteration of the entire coding region and all splice sites of caspase-8 and -10 genes in 99 gastric cancers by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) and sequencing. We found LOH of the caspase-8 and -10 in nine (28%) of 32 and in four (15%) of 26 informative cases, respectively. Overall, three of 99 gastric cancers (3%) were found to have the caspase-10 mutations, which were identi®ed in the coding regions of the death eector domain (codon 147) and the p17 large protease domain (codons 257 and 410), whereas no mutation was detected in caspase-8. In vitro expression studies, the M147T and Q257stop mutants severely impaired caspase-10-mediated apoptosis, whereas the V410I which was the same mutation detected in ALPS patient had a signi®cant, albeit less severe, eect on apoptosis. The data presented here suggest that somatic alterations of the caspase-10 gene might contribute to the pathogenesis in a subset of gastric cancers through the loss of their apoptotic function.

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“…Aberrant methylation of p16 has been frequently detected in many human cancers 4,5,24–29. The p15 gene, adjacent to p16 on chromosome 9p21, is also commonly hypermethylated in human neoplasms, especially among hematopoietic malignancies 24,27–30.…”

Section: Dna Methylation and Cancer Developmentmentioning

confidence: 99%

Epigenetic Tumor Markers in Plasma and Serum

Wong

Johnson

2001

Annals of the New York Academy of Sciences

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Circulating tumor DNA in plasma and serum has been demonstrated to reflect the biological characteristics of tumors, including the rates of apoptosis and necrosis. Aberrant promoter methylation has increasingly emerged as a fundamental molecular abnormality associated with loss of critical gene functions during carcinogenesis. This epigenetic inheritance has significant biological implications for early tumor initiation and cancer progression or metastasis formation. The promoter‐region methylation is crucial in transcriptional silencing of tumor suppressor genes, DNA repair genes, and metastasis inhibitor genes, and is linked to the predisposition of genetic alterations of other cancer‐associated genes. Of clinical relevance, epigenetic markers in plasma and serum have recently been established as specific and sensitive biomarkers for early and noninvasive screening, risk assessment, and monitoring of neoplastic diseases. A panel of epigenetic markers may possibly allow the detection of circulating tumor DNA in virtually all patients with different cancer types. Furthermore, the prognostic value of aberrant DNA methylation and therapeutic implications of demethylation of methylated genes could further improve the management of patients with different kinds of cancer.

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Concurrent disruption of cell cycle associated genes in mantle cell lymphoma: a genotypic and phenotypic study of cyclin D1, p16, p15, p53 and pRb

Cited by 42 publications

References 15 publications

Primary cutaneous B-cell lymphoma: a clinical, histological, phenotypic and genotypic study of 21 cases

Primary cutaneous B-cell lymphoma: a clinical, histological, phenotypic and genotypic study of 21 cases

Inactivating mutations of the caspase-10 gene in gastric cancer

Epigenetic Tumor Markers in Plasma and Serum

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