Screening for TP53 rearrangements in families with the Li–Fraumeni syndrome reveals a complete deletion of the TP53 gene

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).

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Identification and characterization of TP53 gene Allele Dropout in Li-Fraumeni syndrome and Oral cancer cohorts

Scientific Reports ◽

10.1038/s41598-018-30238-7 ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 1

Author(s):

Mohammed Moquitul Haque ◽

Pradnya Kowtal ◽

Rajiv Sarin

Keyword(s):

Oral Cancer ◽

Tp53 Gene ◽

Li Fraumeni Syndrome ◽

Allele Dropout ◽

Li Fraumeni ◽

Identification And Characterization

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

Rare Tumors ◽

10.1177/2036361317749645 ◽

2018 ◽

Vol 10 ◽

pp. 203636131774964 ◽

Cited By ~ 2

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.

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

International Journal of Surgical Pathology ◽

10.1177/1066896919878804 ◽

2019 ◽

Vol 28 (2) ◽

pp. 225-228 ◽

Cited By ~ 3

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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A new germline TP53 gene mutation in a family with Li-Fraumeni syndrome

European Journal of Cancer ◽

10.1016/0959-8049(96)00104-9 ◽

1996 ◽

Vol 32 (8) ◽

pp. 1359-1365 ◽

Cited By ~ 14

Author(s):

B. Dockhorn-dworniczak ◽

J. Wolff ◽

C. Poremba ◽

K.-L. Schäfer ◽

J. Ritter ◽

...

Keyword(s):

Gene Mutation ◽

Tp53 Gene ◽

Li Fraumeni Syndrome ◽

Tp53 Gene Mutation ◽

Li Fraumeni

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Significance of intron 6 sequence variations in the TP53 gene in Li-Fraumeni syndrome

Cancer Genetics and Cytogenetics ◽

10.1016/s0165-4608(01)00428-9 ◽

2001 ◽

Vol 129 (1) ◽

pp. 85-87 ◽

Cited By ~ 8

Author(s):

J.M. Varley ◽

G. McGown ◽

M. Thorncroft ◽

A.M. Kelsey ◽

J.M. Birch

Keyword(s):

Tp53 Gene ◽

Li Fraumeni Syndrome ◽

Sequence Variations ◽

Li Fraumeni

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Choroid plexus carcinoma: review of literature

Russian Journal of Pediatric Hematology and Oncology ◽

10.21682/2311-1267-2020-7-1-51-61 ◽

2020 ◽

Vol 7 (1) ◽

pp. 51-61

Author(s):

A. F. Valiakhmetova ◽

L. I. Papusha ◽

L. A. Yasko ◽

A. E. Druy ◽

S. K. Gorelyshev ◽

...

Keyword(s):

Choroid Plexus ◽

Molecular Genetic ◽

Survival Rates ◽

International Study ◽

Tp53 Gene ◽

Choroid Plexus Carcinoma ◽

Main Role ◽

Genetic Changes ◽

Li Fraumeni Syndrome ◽

Li Fraumeni

Choroid plexus carcinoma (CPC) is a rare malignant tumor arising from the epithelium of the choroid plexus of the brain. More than 80 % of CPCs occur in children. Mutations in the TP53 gene is played the main role in the pathogenesis of these tumors. Choroid plexus carcinomas in 40 % of cases are associated with Li–Fraumeni syndrome. Survival rates in patients with CPC and Li–Fraumeni syndrome are extremely low. The standards of the therapy for patients with CPC are not defined. The extent of surgical resection and treatment modality correlate with prognosis. The role of adjuvant therapy in CPC remains unclear: doses and volumes of radiation therapy (RT), combinations of chemotherapeutic drugs, timing, and a combination of RT and chemotherapy (CT) have not been identified. Also, there is neither a standard CT regimen nor a prospective international study assessing the efficacy and toxicity of various combinations of cytostatics in patients with CPC. The article presents an overview of the existing molecular genetic changes, existing methods for the diagnosis and treatment of choroid plexus carcinoma.

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Metachronic Breast and Cerebellar Neoplasm in a Young Patient

Revista Brasileira de Ginecologia e Obstetrícia / RBGO Gynecology and Obstetrics ◽

10.1055/s-0040-1701456 ◽

2020 ◽

Vol 42 (02) ◽

pp. 114-119

Author(s):

Jéssika de Oliveira Nascimento ◽

Lara Caroline Anastacio Haro ◽

Rafael da Silva Sá ◽

Rebeca Espelho Storch

Keyword(s):

Young Patient ◽

Tp53 Gene ◽

Mucinous Carcinoma ◽

Breast Cancers ◽

Li Fraumeni Syndrome ◽

Cerebellar Neoplasm ◽

Short Period ◽

Dominant Disease ◽

Desmoplastic Medulloblastoma ◽

Li Fraumeni

AbstractSeveral factors trigger the development of genetic mutations that are responsible for causing a neoplasm. Medulloblastoma is a malignant and invasive cerebellar neoplasm, that affects children and young adults. Mucinous carcinoma is a special type of breast cancer. Being a special atypical subtype of invasive carcinoma, it most frequently affects women of advanced age and represents 1 to 7% of all breast cancers. The reported case aims to show the rarity of the occurrence of desmoplastic medulloblastoma and mammary mucinous carcinoma in a young patient in a short period of time, in different sites, without direct anatomical attachment and without occurrence of metastasis. Initially, this patient had a desmoplastic medulloblastoma and was treated with lumpectomy and radiotherapy. After 13 months, the patient was diagnosed with a mucinous breast carcinoma, underwent mastectomy, adjuvant chemotherapy and is currently undergoing endocrinotherapy. We conclude, based on the metachronous characteristic of the neoplasia and clinical characteristics, that the patient is likely to have Li-Fraumeni syndrome, an autosomal dominant disease with mutation of the TP53 gene, which is the the main involved. Because the patient does not present all the characteristics of the phenotype of the syndrome, she can thus be classified as having Li-Fraumeni variant or Li-Fraumeni-like syndrome.

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A Unique Case of Bilateral Thalamic High-Grade Glioma in a Pediatric Patient with LI-Fraumeni Syndrome: Case Presentation and Review of the Literature

Neurology International ◽

10.3390/neurolint13020017 ◽

2021 ◽

Vol 13 (2) ◽

pp. 175-183

Author(s):

Raffaella Messina ◽

Gerardo Cazzato ◽

Teresa Perillo ◽

Vita Stagno ◽

Valeria Blè ◽

...

Keyword(s):

Pathological Condition ◽

High Grade Glioma ◽

Tp53 Gene ◽

High Grade ◽

Pediatric Age ◽

Li Fraumeni Syndrome ◽

Qualitative Systematic Review ◽

History Of ◽

Li Fraumeni ◽

Mesh Database

Li-Fraumeni syndrome (LFS) is a rare high-penetrance and autosomal-dominant pathological condition caused by the germline mutation of the TP53 gene, predisposing to the development of tumors from pediatric age. We conducted a qualitative systematic review following the ENTREQ (Enhancing Transparency in Reporting the Synthesis of Qualitative Research) framework. A search was made in MEDLINE/Pubmed and MeSH Database using the terms “Li-Fraumeni” AND “pediatric high-grade glioma (HGG)”, identifying six cases of HGGs in pediatric patients with LFS. We added a further case with peculiar features such as no familiar history of LFS, association of embryonal rhabdomyosarcoma and bithalamic HGG, whose immunohistochemical profile was accurately defined by Next Generation Sequencing. Knowledge synthesis and case analysis grounded the discussion about challenges in the management of this pathology in pediatric age.

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