scholarly journals Genetic and stochastic influences upon tumor formation and tumor types in Li-Fraumeni mouse models

2020 ◽  
Vol 4 (3) ◽  
pp. e202000952
Author(s):  
Chang S Chan ◽  
Yvonne Sun ◽  
Hua Ke ◽  
Yuhan Zhao ◽  
Merzu Belete ◽  
...  
Keyword(s):  
High Frequency ◽  
Tumor Tissue ◽  
Tumor Formation ◽  
Tissue Type ◽  
Genetic Modifiers ◽  
Stochastic Effects ◽  
Li Fraumeni Syndrome ◽  
Increased Risk ◽  
Li Fraumeni ◽  
Tumor Types

p53 is the most frequently mutated gene in human cancers. Li-Fraumeni syndrome patients inheriting heterozygous p53 mutations often have a much-increased risk to develop cancer(s) at early ages. Recent studies suggest that some individuals inherited p53 mutations do not have the early onset or high frequency of cancers. These observations suggest that other genetic, environmental, immunological, epigenetic, or stochastic factors modify the penetrance of the cancerous mutant Tp53 phenotype. To test this possibility, this study explored dominant genetic modifiers of Tp53 mutations in heterozygous mice with different genetic backgrounds. Both genetic and stochastic effects upon tumor formation were observed in these mice. The genetic background of mice carrying Tp53 mutations has a strong influence upon the tissue type of the tumor produced and the number of tumors formed in a single mouse. The onset age of a tumor is correlated with the tissue type of that tumor, although identical tumor tissue types can occur at very different ages. These observations help to explain the great diversity of cancers in different Li-Fraumeni patients over lifetimes.

Neuroradiology Manifestations of Li-Fraumeni Syndrome: Epidemiology, Genetics, Imaging Findings, and Management

Neurographics ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 228-235
Author(s):  
S. Naganawa ◽  
T. Donohue ◽  
A. Capizzano ◽  
Y. Ota ◽  
J. Kim ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Soft Tissue Sarcomas ◽  
Suppressor Gene ◽  
Imaging Findings ◽  
Li Fraumeni Syndrome ◽  
Increased Risk ◽  
Li Fraumeni ◽  
Risk Of Cancer

Li-Fraumeni syndrome is a familial cancer predisposition syndrome associated with germline mutation of the tumor suppressor gene 53, which encodes the tumor suppressor p53 protein. Affected patients are predisposed to an increased risk of cancer development, including soft-tissue sarcomas, breast cancer, brain tumors, and adrenocortical carcinoma, among other malignancies. The tumor suppressor gene TP53 plays an important, complex role in regulating the cell cycle, collaborating with transcription factors and other proteins. The disruption of appropriate cell cycle regulation by mutated TP53 is considered to be the cause of tumorigenesis in Li-Fraumeni syndrome. Appropriate surveillance, predominantly by using MR imaging, is used for early malignancy screening in an effort to improve the survival rate among individuals who are affected. Patients with Li-Fraumeni syndrome are also at increased risk for neoplasm development after radiation exposure, and, therefore, avoiding unnecessary radiation in both the diagnostic and therapeutic settings is paramount. Here, we review the epidemiology, genetics, imaging findings, and the current standard surveillance protocol for Li-Fraumeni syndrome from the National Comprehensive Cancer Network as well as potential treatment options.Learning Objective: Describe the cause of second primary malignancy among patients with Li-Fraumeni syndrome.

scholarly journals Simultaneous diagnosis of liver PEComa in a family with known Li–Fraumeni syndrome: a case report

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
María del Mar Galera López ◽  
Iván Márquez Rodas ◽  
Carolina Agra Pujol ◽  
Ángela García Pérez ◽  
Enrique Velasco Sánchez ◽  
...  
Keyword(s):  
P53 Protein ◽  
Tumor Development ◽  
Epithelioid Cell ◽  
Hereditary Disease ◽  
Loss Of Function ◽  
Genetic Syndrome ◽  
Li Fraumeni Syndrome ◽  
Perivascular Epithelioid Cell ◽  
Increased Risk ◽  
Li Fraumeni

Abstract Background Li–Fraumeni syndrome (LFS) is an autosomal dominant hereditary disease. It is associated with the loss of function of the p53 protein and an increased risk of malignant tumor development at early age. The most frequently detected tumors include breast cancer, sarcomas, leukemia, brain tumors, and adrenocortical carcinomas. While sarcomas account for only 1% of solid tumors, they are more frequently detected in these families. Case presentation We report a simultaneous diagnosis of hepatic perivascular epithelioid cell tumor (PEComa), a very rare subtype of sarcoma, in two siblings with a LFS. Conclusions The simultaneous diagnosis of PEComa in two siblings presented in this case allowed us to review the frequency of PEComa in this genetic syndrome previously reported, which was very little. Despite its rarity, PEComa must be considered in the differential diagnosis of new-onset liver lesions in patients who were previously diagnosed with LFS.

TP53 PIN3 and MDM2 SNP309 polymorphisms as genetic modifiers in the Li-Fraumeni syndrome: impact on age at first diagnosis

2009 ◽  
Vol 46 (11) ◽  
pp. 766-772 ◽  
Author(s):  
V Marcel ◽  
E I Palmero ◽  
P Falagan-Lotsch ◽  
G Martel-Planche ◽  
P Ashton-Prolla ◽  
...  
Keyword(s):  
Genetic Modifiers ◽  
Mdm2 Snp309 ◽  
Li Fraumeni Syndrome ◽  
Li Fraumeni ◽  
First Diagnosis

scholarly journals Overview of the Clinical Features of Li-Fraumeni Syndrome and the Current European ERN GENTURIS Guideline

2021 ◽  
Author(s):  
Christian Peter Kratz ◽  
Verena Steinke-Lange ◽  
Isabel Spier ◽  
Stefan Aretz ◽  
Evelin Schröck ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Positive Family History ◽  
Reference Network ◽  
Early Age ◽  
Surveillance Programme ◽  
Li Fraumeni Syndrome ◽  
European Reference Network ◽  
Increased Risk ◽  
History Of ◽  
Li Fraumeni

AbstractPatients with a tumour-risk syndrome have a significantly increased risk of developing cancer during their lifetime. A positive family history of tumour disease or an unusually early age of onset may be indicative of a tumour risk syndrome. With the diagnosis of a tumour risk syndrome it is possible to recommend a risk-adapted tumour surveillance programme for the patient and (asymptomatic) family members at risk. This facilitates early detection of possible tumours and thus often prevents advanced tumour stages. Li-Fraumeni syndrome is associated with a significantly increased risk of sarcoma and breast cancer in particular, but it is often not diagnosed clinically in those affected. This article reviews the clinical picture, genetic cause and special aspects in the diagnosis and care of patients with Li-Fraumeni syndrome. The initiative resulted from the European reference network GENTURIS, which has set itself the task of improving the identification and care of patients with tumour risk syndromes. A first step is the recent publication of a European guideline for Li-Fraumeni syndrome, which is summarised here and discussed in the context of existing recommendations.

High frequency of de novo mutations in Li-Fraumeni syndrome

2009 ◽  
Vol 46 (10) ◽  
pp. 689-693 ◽  
Author(s):  
K D Gonzalez ◽  
C H Buzin ◽  
K A Noltner ◽  
D Gu ◽  
W Li ◽  
...  
Keyword(s):  
High Frequency ◽  
De Novo ◽  
De Novo Mutations ◽  
Li Fraumeni Syndrome ◽  
Li Fraumeni

scholarly journals Angiosarcoma in previously irradiated breast in patient with Li-Fraumeni syndrome. A case report

2014 ◽  
Vol 133 (2) ◽  
pp. 151-153 ◽  
Author(s):  
Oséias Vargas Barbosa ◽  
André Borba Reiriz ◽  
Ricardo Antônio Boff ◽  
Willian Passos Oliveira ◽  
Luiza Rossi
Keyword(s):  
Case Report ◽  
Autosomal Dominant ◽  
Ductal Carcinoma ◽  
Epithelioid Angiosarcoma ◽  
Li Fraumeni Syndrome ◽  
Increased Risk ◽  
Li Fraumeni ◽  
The Right ◽  
Surgical Treatments ◽  
Autosomal Dominant Inheritance Pattern

CONTEXT: Li-Fraumeni syndrome is a rare disease with an autosomal dominant inheritance pattern and high penetrance that defines a 50% chance of developing cancer before the age of 30 years, including cases of breast sarcoma. Patients with this syndrome who require radiotherapy have an increased risk of developing secondary malignancies including angiosarcomas. CASE REPORT: This was a case report on a female patient with Li-Fraumeni syndrome. In October 2005, she was diagnosed with invasive ductal carcinoma of the right breast and underwent sectorectomy. She then received chemotherapy and adjuvant radiotherapy. Trastuzumab and tamoxifen were also part of the treatment. She recently sought care at our hospital, complaining of hyperemia and nodulation in the right breast, and underwent surgical resection that revealed epithelioid angiosarcoma. CONCLUSIONS: When genetic predisposition due to Li-Fraumeni syndrome is documented, the therapy should be adapted so as to minimize the risk. Thus, conservative surgical treatments should be avoided and mastectomy without radiation should be prioritized. In cases in which use of radiotherapy is justified, patients should be followed up intensively.

scholarly journals Tissue Type Differences in ABCB1 Expression and Paclitaxel Tissue Pharmacokinetics in Patients With Esophageal Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Ruben A. G. van Eerden ◽  
Leni van Doorn ◽  
Femke M. de Man ◽  
Niels Heersche ◽  
Michail Doukas ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Tumor Tissue ◽  
Treatment Resistance ◽  
Tissue Type ◽  
Esophageal Mucosa ◽  
Tissue Pharmacokinetics ◽  
Esophageal Tissue ◽  
Tumor Types ◽  
Transporter Expression ◽  
Concomitant Radiotherapy

Background: Data from previous work suggests that there is no correlation between systemic (plasma) paclitaxel exposure and efficacy in patients treated for esophageal cancer. In this trial, we investigated ATP-binding cassette efflux transporter expression and intratumoral pharmacokinetics of paclitaxel to identify changes which could be a first sign of chemoresistance.Methods: Patients with esophageal cancer treated with paclitaxel and carboplatin (± concomitant radiotherapy) were included. During the first and last cycle of weekly paclitaxel, blood samples and biopsies of esophageal mucosa and tumor tissue were taken. Changes in paclitaxel exposure and expression of ABCB1 (P-glycoprotein) over time were studied in both tumor tissue and normal appearing esophageal mucosa.Results: ABCB1 was significantly higher expressed in tumor tissue compared to esophageal tissue, during both the first and last cycle of paclitaxel (cycle 1: p < 0.01; cycle 5/6: p = 0.01). Interestingly, ABCB1 expression was significantly higher in adenocarcinoma than in squamous cell carcinoma (p < 0.01). During the first cycle, a trend towards a higher intratumoral paclitaxel concentration was observed compared to the esophageal mucosa concentration (RD:43%; 95%CI: −3% to 111% p = 0.07). Intratumoral and plasma paclitaxel concentrations were significantly correlated during the first cycle (AUC0–48 h: r = 0.72; p < 0.01).Conclusion: Higher ABCB1 expression in tumor tissue, and differences between histological tumor types might partly explain why tumors respond differently to systemic treatment. Resistance by altered intratumoral paclitaxel concentrations could not be demonstrated because the majority of the biopsies taken at the last cycle of paclitaxel did contain a low amount of tumor cells or no tumor.

scholarly journals Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

2021 ◽  
Vol 19 (1) ◽  
pp. 77-102
Author(s):  
Mary B. Daly ◽  
Tuya Pal ◽  
Michael P. Berry ◽  
Saundra S. Buys ◽  
Patricia Dickson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Risk Assessment ◽  
Pancreatic Cancer ◽  
High Risk ◽  
Cancer Syndrome ◽  
Li Fraumeni Syndrome ◽  
Pathogenic Variants ◽  
Increased Risk ◽  
Li Fraumeni ◽  
Familial High Risk

The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic or likely pathogenic variants associated with increased risk of breast, ovarian, and pancreatic cancer and recommended approaches to genetic testing/counseling and management strategies in individuals with these pathogenic or likely pathogenic variants. This manuscript focuses on cancer risk and risk management for BRCA-related breast/ovarian cancer syndrome and Li-Fraumeni syndrome. Carriers of a BRCA1/2 pathogenic or likely pathogenic variant have an excessive risk for both breast and ovarian cancer that warrants consideration of more intensive screening and preventive strategies. There is also evidence that risks of prostate cancer and pancreatic cancer are elevated in these carriers. Li-Fraumeni syndrome is a highly penetrant cancer syndrome associated with a high lifetime risk for cancer, including soft tissue sarcomas, osteosarcomas, premenopausal breast cancer, colon cancer, gastric cancer, adrenocortical carcinoma, and brain tumors.

Li-Fraumeni syndrome and adrenal tumours: case report

2018 ◽  
Author(s):  
Mariana Tome ◽  
Jessica Guarino ◽  
Marta Iturregui
Keyword(s):  
Case Report ◽  
Li Fraumeni Syndrome ◽  
Adrenal Tumours ◽  
Li Fraumeni
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