Revisiting tumor patterns and penetrance in germline TP53 mutation carriers: temporal phases of Li–Fraumeni syndrome
- 1 January 2018
- journal article
- review article
- Published by Ovid Technologies (Wolters Kluwer Health) in Current Opinion in Oncology
- Vol. 30 (1), 23-29
- https://doi.org/10.1097/cco.0000000000000423
Abstract
Germline pathogenic TP53 mutation may predispose to multiple cancers but penetrance and cancer patterns remain incompletely documented. We have analyzed international agency for research on cancer TP53 database to reevaluate age and variant-dependent tumor patterns. Genome-wide studies suggest that germline variants are more frequent than estimated prevalence of Li–Fraumeni syndrome (LFS), suggesting that many carriers of potentially pathogenic mutations may not develop the syndrome. Carriers of a germline TP53 mutation who are detected in a clinical context have a penetrance of 80% at age 70. Penetrance varies according to age, sex and mutation type. Temporal tumor patterns show distinct phases, with childhood phase (0–15 years, 22% of all cancers) characterized by adrenal cortical carcinoma, choroid plexus carcinoma, rhabdomyosarcoma and medulloblastoma; early adulthood phase (16–50 years, 51%) including breast cancer, osteosarcoma, soft tissue sarcomas, leukemia, astrocytoma and glioblastoma, colorectal and lung cancer; late adulthood phase (51–80 years, 27%) including pancreatic and prostate cancer. Germline pathogenic variants in TP53 gene have different consequences according to cell, tissue, context and age. The occurrence of frequent variants in patients with no criteria suggestive of LFS calls for attention in predicting individual risk and highlights the need of additional predictors for assigning carriers to appropriate surveillance programs.Keywords
This publication has 35 references indexed in Scilit:
- TP53p.R337H is a conditional cancer-predisposing mutation: further evidence from a homozygous patientBMC Cancer, 2013
- Li-Fraumeni SyndromeGenes & Cancer, 2011
- Joint effects of germ-line TP53 mutation, MDM2 SNP309, and gender on cancer risk in family studies of Li–Fraumeni syndromeHuman Genetics, 2011
- A Common Molecular Mechanism Underlies Two Phenotypically Distinct 17p13.1 Microdeletion SyndromesAmerican Journal of Human Genetics, 2010
- Detailed haplotype analysis at theTP53locus in p.R337H mutation carriers in the population of Southern Brazil: evidence for a founder effectHuman Mutation, 2009
- Tumor Suppressive Functions of p53Cold Spring Harbor Perspectives in Biology, 2009
- Cytoplasmic functions of the tumour suppressor p53Nature, 2009
- BRCA1, BRCA2 and TP53 mutations in very early-onset breast cancer with associated risks to relativesEuropean Journal Of Cancer, 2006
- GermlineTP53 mutations and Li-Fraumeni syndromeHuman Mutation, 2003
- Screening for TP53 rearrangements in families with the Li–Fraumeni syndrome reveals a complete deletion of the TP53 geneOncogene, 2003