SEOM clinical guideline on heritable TP53-related cancer syndrome (2022)

Abstract

Li-Fraumeni syndrome is caused by heterozygous germline pathogenic variants in the TP53 gene. It involves a high risk of a variety of malignant tumors in childhood and adulthood, the main ones being premenopausal breast cancer, soft tissue sarcomas and osteosarcomas, central nervous system tumors, and adrenocortical carcinomas. The variability of the associated clinical manifestations, which do not always fit the classic criteria of Li-Fraumeni syndrome, has led the concept of SLF to extend to a more overarching cancer predisposition syndrome, termed hereditable TP53-related cancer syndrome (hTP53rc). However, prospective studies are needed to assess genotype–phenotype characteristics, as well as to evaluate and validate risk-adjusted recommendations. This guideline aims to establish the basis for interpreting pathogenic variants in the TP53 gene and provide recommendations for effective screening and prevention of associated cancers in carrier individuals.

Breast Sarcomas, Phyllodes Tumors, and Desmoid Tumors: Turning the Magnifying Glass on Rare and Aggressive Entities

“…Li-Fraumeni syndrome, caused by a heterozygous germline pathogenic variant in the TP53 gene, is one of these syndromes. Evidence suggests that a specific surveillance strategy for Li-Fraumeni cases could improve the 5-year survival rate of individuals undergoing surveillance compared to those not undergoing surveillance [8]. Annual breast magnetic resonance imaging (MRI) may be alternated with whole-body MRI every 6 months, as recommended in the latest clinical guidelines of the Sociedad Española de Oncología Médica (SEOM) [8].…”

Treatment With Antitumor Agents Recommended by Cancer Genome Panel for Uterine Leiomyosarcoma

“…However, the copy number of RB1 -loss exons 18-27 was 0, and no retinoblastoma cases were observed under the age of 30 in the family; therefore, investigating the disease onset was not required (Table 2). The VAF of G187V and K132N, which were detected as PVs in TP53 molecule, was 44.89%; therefore, this TP53 mutation may be a germinal mutation that induces Li-Fraumeni syndrome onset [20]. However, as no family members with osteosarcoma, breast cancer, or soft tissue tumors under the age of 30 were noted, TP53 -G187V, K132N as a genetic cause of Li-Fraumeni syndrome was not considered.…”

Importancia del diagnóstico y la vigilancia de pacientes con predisposición genética al cáncer: A propósito del gen TP53

“…El espectro tumoral es amplio e incluye más frecuentemente a los tumores del sistema nervioso central, carcinoma adrenocortical, osteosarcomas, sarcomas, neoplasias malignas hematológicas y cáncer de mama. Neoplasias raras como tumoraciones de plexos coroideos, leucemia linfoblástica aguda con hipodiploidía, rabdomiosarcoma anaplásico, meduloblastoma subtipo Sonic Hedgehog (SHH) y el osteosarcoma son altamente sugestivos del SLF (1). Por lo tanto, el SLF representa uno de los síndromes de predisposición al cáncer más característicos y conocidos, afectando a los pacientes en cualquier grupo etario.…”

“…Actualmente existen guías de práctica clínica para el manejo y seguimiento de pacientes con SLF (1). Para lograr esto, expertos mundiales establecieron registros de pacientes y familias con SFL, contribuyendo con el conocimiento de qué riesgos existen en las personas que poseen una mutación en el gen TP53, y cómo debía ser su manejo.…”

“…Del total de pacientes con SLF, la mayor morbilidad y pérdida de años de vida a causa de tumores malignos la presentan los pacientes pediátricos. Esto se debe a la presencia de tumores altamente agresivos y recurrentes como el rabdomiosarcoma, leucemia linfoblástica aguda, carcinoma adrenocortical, sarcomas, entre otros (1)(2)(3)5,7). Por lo que la identificación de familias con SLF puede ayudar a detectar a los niños portadores de variantes patogénicas en TP53, y así establecer medidas de diagnóstico precoz, tratamiento oportuno y vigilancia más específica asociada al riesgo de cáncer en estos pacientes.…”