title: Fine-mapping chromosomal loss at 9p21: correlation with prognosis in primary cutaneous diffuse large B-cell lymphoma, leg type.
abstract: Primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL, LT) is the most aggressive type of primary cutaneous B-cell lymphoma. In a recent study on 12 patients it was found that inactivation of CDKN2A by either deletion of 9p21.3 or promoter hypermethylation is correlated with a worse prognosis. In the present EORTC multicenter study, skin biopsies of 64 PCLBCL, LT patients were analyzed by multiplex ligation-dependent probe amplification to validate these previous results and to fine-map the losses in this region. Although no minimal common region of loss could be identified, most homozygous loss was observed in the CDKN2A gene (43 of 64; 67%) encoding p16 and p14ARF. Promoter hypermethylation of p16 and p14ARF was found in six and zero cases, respectively. Survival was markedly different between patients with versus without aberrations in the CDKN2A gene (5-year disease-specific survival 43 versus 70%; P=0.06). In conclusion, our results confirm that deletion of chromosome 9p21.3 is found in a considerable proportion of PCLBCL, LT patients and that inactivation of the CDKN2A gene is associated with an unfavorable prognosis. In most patients the deletion involves a large area of at least several kilobase pairs instead of a small minimal common region.
authors.affiliation: Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands. n.j.senff@lumc.nl
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Senff
authors.forename: Willem H
authors.initials: WH
authors.lastname: Zoutman
authors.forename: Maarten H
authors.initials: MH
authors.lastname: Vermeer
authors.forename: Chalid
authors.initials: C
authors.lastname: Assaf
authors.forename: Emilio
authors.initials: E
authors.lastname: Berti
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Cerroni
authors.forename: Blanca
authors.initials: B
authors.lastname: Espinet
authors.forename: Ricardo Fernandez
authors.initials: RF
authors.lastname: de Misa Cabrera
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Geerts
authors.forename: Werner
authors.initials: W
authors.lastname: Kempf
authors.forename: Tracey J
authors.initials: TJ
authors.lastname: Mitchell
authors.forename: Marco
authors.initials: M
authors.lastname: Paulli
authors.forename: Tony
authors.initials: T
authors.lastname: Petrella
authors.forename: Nicola
authors.initials: N
authors.lastname: Pimpinelli
authors.forename: Marco
authors.initials: M
authors.lastname: Santucci
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Whittaker
authors.forename: Rein
authors.initials: R
authors.lastname: Willemze
authors.forename: Cornelis P
authors.initials: CP
authors.lastname: Tensen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007866:Leg; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015203:Reproducibility of Results; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16