Prevalence of Germline TP53 Mutations in a Prospective Series of Unselected Patients with Adrenocortical Carcinoma

Divisions of Molecular Medicine and Genetics (V.M.R., J.N.E., J.M.L.) and Metabolism, Endocrinology, and Diabetes (T.E., G.D.H.), Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109-5419
The Journal of Clinical Endocrinology and Metabolism (Impact Factor: 6.21). 11/2012; 98(1). DOI: 10.1210/jc.2012-2198
Source: PubMed


Adrenocortical carcinoma (ACC) is a hallmark cancer in families with Li Fraumeni syndrome (LFS) caused by mutations in the TP53 gene. The prevalence of germline TP53 mutations in children diagnosed with ACC ranges from 50-97%. Although existing criteria advocate for TP53 testing in all patients with ACC regardless of age at diagnosis, the overall prevalence of germline mutations in patients diagnosed with ACC has not been well studied.

Patients and methods:
A total of 114 patients with confirmed ACC evaluated in the University of Michigan Endocrine Oncology Clinic were prospectively offered genetic counseling and TP53 genetic testing, regardless of age at diagnosis or family history. Ninety-four of the 114 patients met with a genetic counselor (82.5%), with 53 of 94 (56.4%) completing TP53 testing; 9.6% (nine of 94) declined testing. The remainder (32 of 94; 34%) expressed interest in testing but did not pursue it for various reasons.

Four of 53 patients in this prospective, unselected series were found to have a TP53 mutation (7.5%). The prevalence of mutations in those diagnosed over age 18 was 5.8% (three of 52). There were insufficient data to estimate the prevalence in those diagnosed under age 18. None of these patients met clinical diagnostic criteria for classic LFS. Three of the families met criteria for Li Fraumeni-like syndrome; one patient met no existing clinical criteria for LFS or Li Fraumeni-like syndrome. Three of the four patients with mutations were diagnosed with ACC after age 45.

Genetic counseling and germline testing for TP53 should be offered to all patients with ACC. Restriction on age at diagnosis or strength of the family history would fail to identify mutation carriers.

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    • "The prevalence of germline TP53 mutations in apparently sporadic ACT patients varies according to the age group. While in adults the prevalence is low, between 3–6% according to two recent studies (Herrmann, Heinze et al. 2012, Raymond, Else et al. 2012), among children, this proportion is significantly higher. Data from the USA and Europe indicates that the prevalence of germline TP53 mutations in pediatric patients is ∼50–80% (Wagner, Portwine et al. 1994, Varley, McGown et al. 1999). "
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