Comprehensive analysis of PTEN status in Sezary syndrome.
Sézary syndrome (SS) is an incurable leukemic variant of cutaneous T-cell lymphoma characterized by recurrent chromosomal alterations, among which, chromosome 10q deletion is very frequent. In this study, we investigated the PTEN status, on locus 10q23, in 44 SS patients; our findings show that PTEN is deleted in 36% of SS cases, whereas PTEN downregulation is observed in almost all of the samples evaluated by quantitative reverse-transcriptase polymerase chain reaction and Western blotting analysis. Neither DNA sequence mutation nor promoter hypermethylation were found at the PTEN locus, but we demonstrate that PTEN level can be also reduced by a group of miRs previously found upregulated and of prognostic relevance in SS; particularly, miR-21, miR-106b, and miR-486 were able to control PTEN abundance either in vitro or in vivo. Finally, because reduced PTEN activates the PI3/AKT-mediated pathway of cell growth and survival, we demonstrate that PTEN deficiency is associated with activated AKT in skin resident but not circulating SS cells, suggesting that the cutaneous milieu may strongly contribute to the SS cell growth. To our knowledge, this is the first study fully exploring the PTEN status in a large cohort of SS patients, unveiling potential elements of clinical utility in this malignancy.
Istituto Dermopatico dell'Immacolata-Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy;
Cristina
C
Cristofoletti
Maria Cristina
MC
Picchio
Cristina
C
Lazzeri
Valeria
V
Tocco
Elena
E
Pagani
Antonella
A
Bresin
Barbara
B
Mancini
Francesca
F
Passarelli
Antonio
A
Facchiano
Enrico
E
Scala
Giuseppe Alfonso
GA
Lombardo
Maria
M
Cantonetti
Elisabetta
E
Caprini
Giandomenico
G
Russo
Maria Grazia
MG
Narducci
D000368:Aged; D000369:Aged, 80 and over; D002879:Chromosomes, Human, Pair 10 / Q000648:ultrastructure; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D015536:Down-Regulation; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D051059:PTEN Phosphohydrolase / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D017422:Sequence Analysis, DNA; D012751:Sezary Syndrome / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism / Q000473:pathology
D035683:MicroRNAs; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019869:Phosphatidylinositol 3-Kinases; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human