RGD Reference Report - CDKN2A-CDKN2B deletion defines an aggressive subset of cutaneous T-cell lymphoma. - Rat Genome Database

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CDKN2A-CDKN2B deletion defines an aggressive subset of cutaneous T-cell lymphoma.

Authors: Laharanne, E  Chevret, E  Idrissi, Y  Gentil, C  Longy, M  Ferrer, J  Dubus, P  Jouary, T  Vergier, B  Beylot-Barry, M  Merlio, JP 
Citation: Laharanne E, etal., Mod Pathol. 2010 Apr;23(4):547-58. doi: 10.1038/modpathol.2009.196. Epub 2010 Jan 29.
RGD ID: 8552306
Pubmed: PMID:20118908   (View Abstract at PubMed)
DOI: DOI:10.1038/modpathol.2009.196   (Journal Full-text)

Inactivation of the CDKN2A-CDKN2B locus has been reported in the most frequent subtypes of cutaneous T-cell lymphomas (CTCLs), mycosis fungoides, Sezary syndrome (SS) and CD30+ cutaneous anaplastic large cell lymphoma. To investigate whether genetic or epigenetic inactivation of CDKN2A-CDKN2B is more specifically observed in certain CTCL subtypes with clinical impact, we used array-comparative genomic hybridization, quantitative PCR, interphase fluorescent in situ hybridization and methylation analyses of p14(ARF) p16(INK4A) and p15(INK4B) promoters. We studied 67 samples from 58 patients with either transformed mycosis fungoides (n=24), SS (n=16) or CD30+ cutaneous anaplastic large cell lymphoma (n=18). We observed combined CDKN2A-CDKN2B deletion in both transformed mycosis fungoides (n=17, 71%) and SS patients (n=7, 44%), but, surprisingly, in only one CD30+ cutaneous anaplastic large cell lymphoma case. Interphase fluorescent in situ hybridization showed 9p21 loss in 17 out of 19 cases, with 9p21 deletion indicating either hemizygous (n=4) or homozygous (n=2) deletion, with mixed patterns in most patients (n=11). The limited size of 9p21 deletion was found to account for false-negative detection by either BAC arrays (n=9) or fluorescent in situ hybridization (n=2), especially in patients with Sezary syndrome (n=6). Methylation was found to be restricted to the p15(INK4B) gene promoter in patients with or without 9p21 deletion and did not correlate with prognosis. In contrast, CDKN2A-CDKN2B genetic loss was strongly associated with a shorter survival in CTCL patients (P=0.002) and more specifically at 24 months in transformed mycosis fungoides and SS patients (P=0.02). As immunohistochemistry for p16(INK4A) protein was not found to be informative, the genetic status of the CDKN2A-CDKN2B locus would be relevant in assessing patients with epidermotropic CTCLs in order to identify those cases where the disease was more aggressive.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CDKN2AHumanprimary cutaneous T-cell non-Hodgkin lymphoma disease_progressionIAGP DNA:deletion (human)RGD 
CDKN2BHumanprimary cutaneous T-cell non-Hodgkin lymphoma disease_progressionIAGP DNA:deletion (human)RGD 
Cdkn2aRatprimary cutaneous T-cell non-Hodgkin lymphoma disease_progressionISOCDKN2A (Homo sapiens)DNA:deletion (human)RGD 
Cdkn2aMouseprimary cutaneous T-cell non-Hodgkin lymphoma disease_progressionISOCDKN2A (Homo sapiens)DNA:deletion (human)RGD 
Cdkn2bRatprimary cutaneous T-cell non-Hodgkin lymphoma disease_progressionISOCDKN2B (Homo sapiens)DNA:deletion (human)RGD 
Cdkn2bMouseprimary cutaneous T-cell non-Hodgkin lymphoma disease_progressionISOCDKN2B (Homo sapiens)DNA:deletion (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CDKN2AHumanLymphoma disease_progressionIAGP DNA:deletionRGD 
CDKN2BHumanLymphoma disease_progressionIAGP DNA:deletionRGD 
Objects Annotated

Genes (Rattus norvegicus)
Cdkn2a  (cyclin-dependent kinase inhibitor 2A)
Cdkn2b  (cyclin-dependent kinase inhibitor 2B)

Genes (Mus musculus)
Cdkn2a  (cyclin dependent kinase inhibitor 2A)
Cdkn2b  (cyclin dependent kinase inhibitor 2B)

Genes (Homo sapiens)
CDKN2A  (cyclin dependent kinase inhibitor 2A)
CDKN2B  (cyclin dependent kinase inhibitor 2B)


Additional Information