Pregled priporočil za genetsko in preventivno obravnavo pacientov s sindromom Li-Fraumeni An overview of recommendations for genetic and preventive management of patients with Li-Fraumeni syndrome

Abstract

Zarodne patogene različice v genu TP53 povezujemo z dedno predispozicijo za razvoj raka. Najbolj penetrantne med njimi povezujemo s klinično sliko sindroma Li-Fraumeni (LFS). V pričujočem prispevku želimo predstaviti genetsko ozadje in klinične značilnosti sindroma ter priporočila za genetsko testiranje in preventivno spremljanje posameznikov z LFS. Gre za redek dedni sindrom, povezujemo pa ga s širokim naborom različnih rakov, ki se pojavljajo v vseh starostnih obdobjih – med njimi so najpogostejši: karcinom skorje nadledvične žleze, rak dojk, tumorji centralnega živčnega sistema, osteosarkom in sarkomi mehkih tkiv. Beljakovinski produkt gena TP53 sodeluje v številnih celičnih procesih, med drugim pri popravljanju napak v DNK, nastalih med delitvijo celic, in pri programirani celični smrti. Razumevanje sindroma in klinična obravnava ljudi z LFS je od njegove prve opredelitve do danes močno napredovala. Vzporedno s tem se z leti spreminjajo indikacije in metode genetskega testiranja. Preventivno spremljanje po potrditvi LFS je zelo intenzivno in vključuje letne preiskave celega telesa z magnetno resonanco. Namen spremljanja je z zgodnjim odkrivanjem malignih sprememb omogočiti čim uspešnejše zdravljenje, kar vodi do boljšega preživetja in kakovosti življenja ljudi z LFS. Pacienti z diagnozo LFS, ki so bili v letih 2015–2026 obravnavani na Onkološkem inštitutu Ljubljana, so se v veliki večini odločili za spremljanje v skladu s preventivnimi priporočili in priporočila tudi dolgoročno upoštevajo.

Abstract (Eng)

Germline pathogenic variants in the TP53 gene are associated with an increased risk of developing cancer. The most penetrant of these variants are associated with Li-Fraumeni syndrome (LFS), a rare hereditary cancer predisposition syndrome. In this overview, we aim to present the genetic causes and clinical characteristics of the syndrome, as well as recommendations for genetic testing and preventive surveillance in individuals with LFS. This predisposition has been linked to a wide variety of tumours, which occur in all age groups, the most common being adrenocortical carcinoma, breast cancer, central nervous system tumours, osteosarcoma, and soft tissue sarcoma. The protein product of the TP53 gene is involved in many cellular processes, including the repair of replication errors accumulated during cell division and programmed cell death. Our understanding of the syndrome and management of individuals with LFS has progressed greatly since it was first described. In parallel, indications and methods for performing genetic testing have also evolved over the years. Preventive surveillance after diagnosis of LFS is very intensive and includes yearly whole-body magnetic resonance imaging. Its aim is to enable better treatment through early detection of malignant tumours, which leads to improved survival and quality of life for individuals with LFS. The majority of patients with LFS seen at the Institute of Oncology Ljubljana in the years 2015–2026 opted for surveillance in accordance with the guidelines and managed to adhere to their preventive programmes.