The TP53 gene promoter is not methylated in families suggestive of Li-Fraumeni syndrome with no germline TP53 mutations

2009 ◽  
Vol 193 (1) ◽  
pp. 63-66 ◽  
Author(s):  
Alena Finkova ◽  
Alzbeta Vazna ◽  
Ondrej Hrachovina ◽  
Sarka Bendova ◽  
Kamila Prochazkova ◽  
...  
Keyword(s):  
Gene Promoter ◽  
Tp53 Gene ◽  
Tp53 Mutations ◽  
Li Fraumeni Syndrome ◽  
Li Fraumeni

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

2013 ◽  
Vol 98 (1) ◽  
pp. E119-E125 ◽  
Author(s):  
Victoria M. Raymond ◽  
Tobias Else ◽  
Jessica N. Everett ◽  
Jessica M. Long ◽  
Stephen B. Gruber ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Family History ◽  
Adrenocortical Carcinoma ◽  
Genetic Counselor ◽  
Tp53 Gene ◽  
Age At Diagnosis ◽  
Tp53 Mutations ◽  
Li Fraumeni Syndrome ◽  
Clinical Criteria ◽  
Li Fraumeni

Abstract 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.

scholarly journals Li-Fraumeni Syndrome and p53 in 2015: Celebrating their Silver Anniversary

2016 ◽  
Vol 39 (1) ◽  
pp. 37 ◽  
Author(s):  
David Malkin
Keyword(s):  
Wilms Tumor ◽  
Cancer Genetics ◽  
Tp53 Gene ◽  
Pleuropulmonary Blastoma ◽  
Li Fraumeni Syndrome ◽  
Von Hippel Lindau ◽  
Von Hippel Lindau Disease ◽  
Li Fraumeni ◽  
Sick Children ◽  
Risk Of Cancer

In a typical morning in the Cancer Genetics Clinic at The Hospital for Sick Children in Toronto, the following array of patients and families might be seen: a family of three children, all harbouring a mutation of the succinyl dehydrogenase C gene inherited from their father who had had extensive surgery several years ago for a secreting paraganglioma; three families with Li-Fraumeni syndrome, each with at least one child harbouring a TP53 gene mutation conferring a lifetime risk of cancer approaching 100% and currently undergoing surveillance for early tumour detection; two children with Li-Fraumeni syndrome undergoing treatment for cancer – one having had three cancer diagnoses before 19 months of age and the other just completing therapy for metastatic adrenocortical carcinoma at age 3; two children with von Hippel-Lindau disease being monitored for persistent pancreatic neuroendocrine tumors and cerebellar hemangioblastomas, respectively; and one child with Beckwith-Wiedeman syndrome and Wilms tumor and another child completing therapy for a pleuropulmonary blastoma (PPB).

Germ-Line TP53 Mutations in Finnish Cancer Families Exhibiting Features of the Li-Fraumeni Syndrome and Negative for BRCA1 and BRCA2

1999 ◽  
Vol 112 (1) ◽  
pp. 9-14 ◽  
Author(s):  
Pia Huusko ◽  
Katariina Castrén ◽  
Virpi Launonen ◽  
Ylermi Soini ◽  
Kati Pääkkönen ◽  
...  
Keyword(s):  
Germ Line ◽  
Brca1 And Brca2 ◽  
Tp53 Mutations ◽  
Li Fraumeni Syndrome ◽  
Li Fraumeni

The first two confirmed sub-Saharan African families with germline TP53 mutations causing Li-Fraumeni syndrome

2018 ◽  
Vol 17 (4) ◽  
pp. 607-613 ◽  
Author(s):  
Shelley Macaulay ◽  
Quintin Clive Goodyear ◽  
Mia Kruger ◽  
Wenlong Chen ◽  
Fahmida Essop ◽  
...  
Keyword(s):  
Tp53 Mutations ◽  
Li Fraumeni Syndrome ◽  
Li Fraumeni ◽  
Sub Saharan ◽  
African Families

scholarly journals Efficacy of oral metformin in a patient with metastatic adrenocortical carcinoma: Examination of mechanisms and therapeutic implications

Rare Tumors ◽  
2018 ◽  
Vol 10 ◽  
pp. 203636131774964 ◽  
Author(s):  
RD Peixoto ◽  
LM Gomes ◽  
TT Sousa ◽  
DJ Racy ◽  
M Shigenaga ◽  
...  
Keyword(s):  
Adrenocortical Carcinoma ◽  
Tp53 Mutation ◽  
Germ Line ◽  
Objective Response ◽  
Tp53 Gene ◽  
Li Fraumeni Syndrome ◽  
Therapeutic Implications ◽  
Treatment Regimens ◽  
First Line Therapy ◽  
Li Fraumeni

Although rare, adrenocortical carcinoma is among the most common tumors found in children with Li-Fraumeni syndrome and Li-Fraumeni-like syndrome, associated with germ-line mutations in the TP53 gene. In southern Brazil, one form of Li-Fraumeni syndrome, associated with childhood adrenocortical carcinoma, is caused by a mutation in the R337H TP53 tetramerisation domain and is attributed to a familial founder effect. Adrenocortical carcinoma is considered an aggressive neoplasm, usually of poor prognosis and is generally unresponsive to systemic chemotherapy. Optimal treatment regimens remain to be established. We report the case of a young woman with metastatic adrenocortical carcinoma, who achieved stable disease with mitotane, cisplatin, doxorubicin, and etoposide as first-line therapy, but then had an objective response to oral metformin that lasted 9 months. The presence of the R337H TP53 mutation suggests a mechanism for the observed response to metformin.

Recurrent Pleomorphic Myxoid Liposarcoma in a Patient With Li-Fraumeni Syndrome

2019 ◽  
Vol 28 (2) ◽  
pp. 225-228 ◽  
Author(s):  
Somaye Y. Zare ◽  
Mariah Leivo ◽  
Oluwole Fadare
Keyword(s):  
Young Patients ◽  
B Cell Lymphoma ◽  
Myxoid Liposarcoma ◽  
Tp53 Gene ◽  
Anterior Chest Wall ◽  
Second Primary ◽  
Mdm2 Gene ◽  
Li Fraumeni Syndrome ◽  
First Case ◽  
Li Fraumeni

Pleomorphic myxoid liposarcoma is an extremely rare, clinically aggressive subtype of liposarcoma that has been primarily reported in young patients. In this article, we report a case of a pleomorphic myxoid liposarcoma that presented as a second primary neoplasm in a 34-year-old man with history of primary mediastinal large B-cell lymphoma. During the clinical workup, the patient was diagnosed with a germline TP53 gene mutation and Li-Fraumeni syndrome. The tumor, a 2.9 × 2.3 × 2.0 cm well-demarcated and solid mass, was centered in the anterior chest wall soft tissue. Histologically, most of the tumor displayed abundantly myxoid stroma, low cellularity of mostly bland spindle cells, delicate branching capillaries, and lipoblasts; these areas transitioned to small areas whose features were reminiscent of pleomorphic liposarcoma. As assessed by fluorescence in situ hybridization, the tumor showed no DDIT3 ( CHOP) (12q13) rearrangements or MDM2 gene amplification. Clinically, the tumor progressed with multiple recurrences and metastasis to the humerus bone. To our knowledge, this is the first case of pleomorphic myxoid liposarcoma diagnosed in an adult with Li-Fraumeni syndrome.

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