Recurrent genomic aberrations combined with deletions of various tumour suppressor genes may deregulate the G1/S transition in CD4+CD56+ haematodermic neoplasms and contribute to the aggressiveness of the disease.
CD4+CD56+ haematodermic neoplasms (HDN) constitute a rare disease characterized by aggressive clinical behaviour and a poor prognosis. Tumour cells from HDN are leukaemic counterparts of plasmacytoid dendritic cells (pDCs). Despite increased knowledge of the ontogenetic origin of these tumours, the genetic causes and oncogenic signalling events involved in malignant transformation are still unknown. To delineate novel candidate regions and disease-related genes, we studied nine typical CD4+CD56+ HDN cases using genome-wide high-resolution array comparative genomic hybridization (CGH). Genomic imbalances, which were predominantly losses, were frequently detected. Gross genomic losses or gains involving an entire chromosome were observed in eight cases. The most frequent imbalances were deletions of chromosome 9, chromosome 13 and partial losses affecting 17p or 12p. Combinations of deletions of tumour suppressor genes (TSG), namely RB1, CDKN1B (p27), CDKN2A, (p16(ink4a), p14(arf)) or TP53 (p53), were observed in all cases. These results indicate that deletion events altering G1/S regulation are crucial for HDN oncogenesis. Furthermore, in addition to frequent sporadic gene losses, in one case we observed a 8q24 interstitial deletion that brought MYC closer to miR-30b/miR-30d, which may be related to their deregulation. Taken together, these results indicate that in addition to frequent G1/S checkpoint alterations, various genetic events could contribute to the chemoresistance of the tumour.
Jardin
F
F
INSERM, U918, European Institute of Peptide Research (IFR23), Centre Henri Becquerel, Rouen, France. fabrice.jardin@rouen.fnclcc.fr
Callanan
M
M
Penther
D
D
Ruminy
P
P
Troussard
X
X
Kerckaert
J P
JP
Figeac
M
M
Parmentier
F
F
Rainville
V
V
Vaida
I
I
Bertrand
P
P
Duval
A B
AB
Picquenot
J M
JM
Chaperot
L
L
Marolleau
J P
JP
Plumas
J
J
Tilly
H
H
Bastard
C
C
D000328:Adult; D000368:Aged; D015704:CD4 Antigens; D019002:CD56 Antigen; D002869:Chromosome Aberrations; D002881:Chromosomes, Human, Pair 12; D002882:Chromosomes, Human, Pair 13; D002886:Chromosomes, Human, Pair 17; D002899:Chromosomes, Human, Pair 9; D055028:Comparative Genomic Hybridization; D005260:Female; D016193:G1 Phase / Q000235:genetics*; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016196:S Phase / Q000235:genetics
D015704:CD4 Antigens; D019002:CD56 Antigen