PURPOSE: 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. RESULTS: 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. CONCLUSIONS: 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.
PURPOSE: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. RESULTS: 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. CONCLUSIONS: 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.
Authors: A Chompret; A Abel; D Stoppa-Lyonnet; L Brugiéres; S Pagés; J Feunteun; C Bonaïti-Pellié Journal: J Med Genet Date: 2001-01 Impact factor: 6.318
Authors: Magali Olivier; Ros Eeles; Monica Hollstein; Mohammed A Khan; Curtis C Harris; Pierre Hainaut Journal: Hum Mutat Date: 2002-06 Impact factor: 4.878
Authors: Anne-Renee Hartman; Rajesh R Kaldate; Lisa M Sailer; Lisa Painter; Charles E Grier; Robbin R Endsley; Marlena Griffin; Stephanie A Hamilton; Cynthia A Frye; Mark A Silberman; Richard J Wenstrup; John F Sandbach Journal: Cancer Date: 2011-10-05 Impact factor: 6.860
Authors: R C Ribeiro; F Sandrini; B Figueiredo; G P Zambetti; E Michalkiewicz; A R Lafferty; L DeLacerda; M Rabin; C Cadwell; G Sampaio; I Cat; C A Stratakis; R Sandrini Journal: Proc Natl Acad Sci U S A Date: 2001-07-31 Impact factor: 11.205
Authors: A C Latronico; E M Pinto; S Domenice; M C Fragoso; R M Martin; M C Zerbini; A M Lucon; B B Mendonca Journal: J Clin Endocrinol Metab Date: 2001-10 Impact factor: 5.958
Authors: F P Li; J F Fraumeni; J J Mulvihill; W A Blattner; M G Dreyfus; M A Tucker; R W Miller Journal: Cancer Res Date: 1988-09-15 Impact factor: 12.701
Authors: A Chompret; L Brugières; M Ronsin; M Gardes; F Dessarps-Freichey; A Abel; D Hua; L Ligot; M G Dondon; B Bressac-de Paillerets; T Frébourg; J Lemerle; C Bonaïti-Pellié; J Feunteun Journal: Br J Cancer Date: 2000-06 Impact factor: 7.640
Authors: Tobias Else; Alex C Kim; Aaron Sabolch; Victoria M Raymond; Asha Kandathil; Elaine M Caoili; Shruti Jolly; Barbra S Miller; Thomas J Giordano; Gary D Hammer Journal: Endocr Rev Date: 2013-12-20 Impact factor: 19.871
Authors: Karen H Lu; Marie E Wood; Molly Daniels; Cathy Burke; James Ford; Noah D Kauff; Wendy Kohlmann; Noralane M Lindor; Therese M Mulvey; Linda Robinson; Wendy S Rubinstein; Elena M Stoffel; Carrie Snyder; Sapna Syngal; Janette K Merrill; Dana Swartzberg Wollins; Kevin S Hughes Journal: J Clin Oncol Date: 2014-02-03 Impact factor: 44.544
Authors: Jonathan D Wasserman; Ana Novokmet; Claudia Eichler-Jonsson; Raul C Ribeiro; Carlos Rodriguez-Galindo; Gerard P Zambetti; David Malkin Journal: J Clin Oncol Date: 2015-01-12 Impact factor: 44.544
Authors: Crystal D C Kamilaris; Fady Hannah-Shmouni; Constantine A Stratakis Journal: Best Pract Res Clin Endocrinol Metab Date: 2020-05-23 Impact factor: 4.690
Authors: Victoria M Raymond; Jessica N Everett; Larissa V Furtado; Shanna L Gustafson; Chelsy R Jungbluth; Stephen B Gruber; Gary D Hammer; Elena M Stoffel; Joel K Greenson; Thomas J Giordano; Tobias Else Journal: J Clin Oncol Date: 2013-07-22 Impact factor: 44.544