Libè Rossella, Groussin Lionel, Tissier Frédérique, Elie Caroline, René-Corail Fernande, Fratticci Amato, Jullian Eric, Beck-Peccoz Paolo, Bertagna Xavier, Gicquel Christine, Bertherat Jérôme
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.
Clin Cancer Res. 2007 Feb 1;13(3):844-50. doi: 10.1158/1078-0432.CCR-06-2085.
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.
TP53 somatic mutations, intragenic LOH (VNTR1 marker), and p53 overexpression were studied in 36 adrenocortical tumors with 17p13 LOH determined by Southern blot.
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).
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.
17p13位点的等位基因缺失[杂合性缺失（LOH）]在肾上腺皮质癌中很常见（85%）。肿瘤抑制基因TP53位于17p13。本研究的目的是确定17p13 LOH的肾上腺皮质肿瘤中TP53体细胞失活突变的频率及其临床生物学相关性。
对36例经Southern印迹法确定存在17p13 LOH的肾上腺皮质肿瘤进行TP53体细胞突变、基因内LOH（VNTR1标记）和p53过表达研究。
33%的肿瘤检测到TP53突变，44%的病例存在VNTR1 LOH，且并不总是与TP53突变的存在相关。只有TP53突变型肿瘤表现出强烈的核免疫反应性。TP53突变型肿瘤明显大于野生型TP53肿瘤（肿瘤中位重量：640克对185克；P = 0.02），与肿瘤进展的更晚期相关（MacFarlane分期IV期；P = 0.01），且无病生存期更短（P = 0.03）。
仅有少数17p13 LOH的肾上腺皮质肿瘤存在VNTR1 LOH或TP53突变，这一发现表明TP53可能不是17p13上参与肾上腺皮质癌进展的唯一或主要肿瘤抑制基因。我们认为，肾上腺皮质癌发生早期17p13区域的基因不稳定性涉及该区域的各种基因。TP53可能只是其中之一，其因失活突变而改变与更具侵袭性肿瘤的发生有关。
