Inactivation of the APC Gene is Constant in Adrenocortical Tumors from Patients with Familial Adenomatous Polyposis but not Frequent in Sporadic Adrenocortical Cancers | oneFAPvoice

welcome to oneFAPvoice

- a positively charged Familial Adenomatous Polyposis community.
  • join today!
scientific articles

Inactivation of the APC Gene is Constant in Adrenocortical Tumors from Patients with Familial Adenomatous Polyposis but not Frequent in Sporadic Adrenocortical Cancers

key information

source: Clinical cancer research

year: 2010

authors: Gaujoux S, Pinson S, Gimenez-Roqueplo A P, Amar L, Ragazzon B, Launay P, Meatchi T, Libé R, Bertagna X, Audebourg A, Zucman-Rossi J, Tissier F, Bertherat J

summary/abstract:

PURPOSE : In adrenocortical tumors (ACT), Wnt/β-catenin pathway activation can be explained by β-catenin somatic mutations only in a subset of tumors. ACT is observed in patients with familial adenomatous polyposis (FAP) with germline APC mutations, as well as in patients with Beckwith-Wiedemann syndrome with Wilms’ tumors reported to have WTX somatic mutations. Both APC and WTX are involved in Wnt/β-catenin pathway regulation and may play a role in ACT tumorigenesis. The aim of this study was to report if APC and WTX may be associated with FAP-associated and sporadic ACT.

EXPERIMENTAL DESIGN : ACTs from patients with FAP and sporadic adrenocortical carcinomas (ACC) with abnormal β-catenin localization on immunohistochemistry but no somatic β-catenin mutations were studied. APC was analyzed by denaturing high-performance liquid chromatography followed by direct sequencing and by multiplex ligation-dependent probe amplification when allelic loss was suspected. WTX was studied by direct sequencing.

RESULTS : Four ACTs were observed in three patients with FAP and were ACC, adrenocortical adenoma, and bilateral macronodular adrenocortical hyperplasia, all with abnormal β-catenin localization. Biallelic inactivation of APC was strongly suggested by the simultaneous existence of somatic and germline alterations in all ACTs. In the 20 sporadic ACCs, a silent heterozygous somatic mutation as well as a rare heterozygous polymorphism in APC was found. No WTX mutations were observed.

CONCLUSIONS : ACT should be considered a FAP tumor. Biallelic APC inactivation mediates activation of the Wnt/β-catenin pathway in the ACTs of patients with FAP. In contrast, APC and WTX genetic alterations do not play a significant role in sporadic ACC.

organization: Université Paris Descartes-Faculté de médecine

DOI: 10.1158/1078-0432.CCR-10-1497

read more full text source

expertly curated content related to this topic

The cookie settings on this website are set to "allow cookies" to give you the best browsing experience possible. If you continue to use this website without changing your cookie settings or you click "Accept" below then you are consenting to this.

Close