Somatic TP53 mutations are relatively rare among adrenocortical cancers with the frequent 17p13 loss of heterozygosity.
OBJECTIVE
Allelic losses [loss of heterozygosity (LOH)] at the 17p13 locus are frequent (85%) in adrenocortical cancers. The tumor suppressor gene TP53 is located at 17p13. The aim of the study was to determine the frequency of TP53 somatic inactivating mutations in adrenocortical tumors with 17p13 LOH and their clinico-biological correlations.


METHODS
TP53 somatic mutations, intragenic LOH (VNTR1 marker), and p53 overexpression were studied in 36 adrenocortical tumors with 17p13 LOH determined by Southern blot.


RESULTS
TP53 mutations were detected in 33% of the tumors, and VNTR1 LOH was present in 44% of the cases and did not always correlate with the presence of a TP53 mutation. Only the TP53-mutant tumors exhibit a strong nuclear immunoreactivity. TP53-mutant tumors were significantly larger than wild-type TP53 tumors (median tumor weight: 640 versus 185 g; P=0.02), were associated with a more advanced stage of tumor progression (MacFarlane stage IV; P=0.01), and had a shorter disease-free survival (P=0.03).


CONCLUSIONS
The finding that only a minority of adrenocortical tumors with 17p13 LOH had either a VNTR1 LOH or a TP53 mutation indicates that TP53 might not be the only or major tumor suppressor gene at 17p13 involved in adrenocortical cancer progression. We suggest that a genetic instability of the 17p13 region, occurring early in adrenocortical cancer development, involves various genes located in this region. TP53 might be only one of them, and its alteration by the occurrence of inactivating mutation is associated with the development of more aggressive tumors.
Libè
Rossella
R
Institut National de la Sante et de la Recherche Medicale U567, Centre National de la Recherche Scientifique UMR8104, Université Paris 5, and Assitance Publique-Hôpitaux de Paris, France.
Groussin
Lionel
L
Tissier
Frédérique
F
Elie
Caroline
C
René-Corail
Fernande
F
Fratticci
Amato
A
Jullian
Eric
E
Beck-Peccoz
Paolo
P
Bertagna
Xavier
X
Gicquel
Christine
C
Bertherat
Jérôme
J
D000306:Adrenal Cortex Neoplasms / Q000235:genetics*; D000328:Adult; D000483:Alleles; D002886:Chromosomes, Human, Pair 17; D018450:Disease Progression; D005260:Female; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics*; D009154:Mutation; D012334:RNA, Neoplasm / Q000737:chemistry
D012334:RNA, Neoplasm