Neurosurgery notes/Tumours/Tumour syndrome/Li-Fraumeni syndrome

Li-Fraumeni syndrome

View Details
Status
Done
logo
Parent item
Tumour syndrome

General

  • Autosomal dominant
  • Disorder of children and young adults
  • Tumours associated
    • CNS tumors
      • Show a bimodal age distribution:
        • In children:
          • Primarily medulloblastomas & related embryonal tumors
          • Choroid plexus carcinoma
        • In age 20–40: primarily astrocytic neoplasms
      • Soft-tissue sarcomas (main)
      • Osteosarcomas,
      • Breast cancer brain tumors and
      • Adrenocortical carcinoma.
  • Caused by a germline mutation in the TP53 tumor suppressor gene (chr 17p13).
    • Multifunctional transcription factor involved in the control of
      • Cell cycle progression,
      • DNA integrity,
      • Survival of cells exposed to DNA-damaging agents and non-genotoxic stimuli such as hypoxia

Numbers

  • Rare (< 400 families identified)
  • Germline T53 mutation
    • 1/5k-20k birth
    • Account for 17% of all familial cancer
BREAST (30.6%) SOFT TSSUES (138%) BRAIN (13%) ADRENAL GLAND (11.7%) BONES (8.6%) HEMATOP. SYSTEM (2.7) (2.5%) LUNG (2.5%) COLON (2.1%) OVARY (19%) STOMACH (1.4%) Others (93%) -30 22 yrs 18 yrs 7 yrs 24 yrs 144 yrs 39 yrs 40 yrs 39 yrs 17 yrs 34 yrs a Females 20 70 120 170 220 270 • Ma les 320 370 34 yrs 420 Tumour counts Fig. 16.20 Target organs for tumorigenesis in 1350 patients carrying a TP53 germline mutation
Target organs for tumorigenesis in 1350 patients carrying a TP53 germline mutation.

3 sets of diagnostic criteria

Classic clinical criteria: to identify an affected individual in a family affected by LFS, Need all 3

  • Sarcoma < 45 years,
  • ≥1 first-degree relative with any tumour < 45 years,
  • A second- or first-degree relative with cancer < 45 years or a sarcoma at any age

LFL-E2 definition (the second definition by Eeles)

  • Sarcoma at any age in the proband,
  • Plus any two of the following tumours within the family (including within a single individual):
    • Breast cancer at < 50 years,
    • Brain tumour,
    • Leukaemia,
    • Adrenocortical tumour,
    • Melanoma,
    • Prostate cancer,
    • Pancreatic cancer at < 60 years, or
    • Sarcoma at any age

LFL-B definition

  • Any childhood cancer or sarcoma, brain tumour, or adrenocortical carcinoma at < 45 years in the proband,
  • Plus one first- or second-degree relative with a cancer typically associated with LFS (i.e. sarcoma, breast cancer, brain tumour, leukaemia, or adrenocortical carcinoma) at any age,
  • Plus one first- or second-degree relative in the same lineage with any cancer diagnosed at an age of < 60 years

Chompret criteria: used to identify who needs genetic testing

  • Familial presentation:
    • Proband with tumor belonging to LFS tumor spectrum (eg, premenopausal breast cancer, soft tissue sarcoma, osteosarcoma, CNS tumor, adrenocortical carcinoma) before age 46 years, AND at least one first or second-degree relative with LFS tumor (except breast cancer if proband has breast cancer) before age 56 years or with multiple tumors;
  • Multiple primary tumors:
    • Proband with multiple tumors (except multiple breast tumors), two of which belong to LFS tumor spectrum and first of which occurred before age 46 years;
  • Rare tumors:
    • Patient with adrenocortical carcinoma, choroid plexus tumor, or rhabdomyosarcoma of embryonal anaplastic subtype, irrespective of family history;
  • Early-onset breast cancer:
    • Breast cancer before age 31 yr.