Table 1 Recommendations for TP53 gene germline variants testing (2020) [10]

Recommendation 1

Patients meeting the modified Chompret criteria:

— Familial presentation: proband with a TP53 core tumor (breast cancer, soft-tissue sarcoma, osteosarcoma, central nervous system tumor, adrenocortical carcinoma) before 46 y.o. AND at least one first- or second-degree relative with a core tumor before 56 y.o. or

- Multiple primitive tumors: proband with multiple tumors, including 2 TP53 core tumors, the first of which occurred before 46 y.o., irrespective of family history; or—Rare tumors: patient with adrenocortical carcinoma, choroid plexus carcinoma, or rhabdomyosarcoma of embryonal anaplastic subtype, irrespective of family history; or

- Very early-onset breast cancer: Breast cancer before 31 y.o.,

irrespective of family history

Recommendation 2

Children and adolescents should be tested for germline TP53

variants if presenting with:

• Hypodiploid acute lymphoblastic leukemia (ALL); or

• Otherwise unexplained sonic hedgehog-driven medulloblastoma; or

• Jaw osteosarcoma

Recommendation 3

Patients who develop a second primary tumor, within the radiotherapy field of a first core TP53 tumor which occurred before 46 y.o., should be tested for germline TP53 variants

Recommendation 4

a. Patients older than 46 y.o. presenting with breast cancer without personal or familial history fulfilling the Chompret Criteria should not be tested for germline TP53 variants

b. Any patient presenting with isolated breast cancer and not fulfilling the Chompret Criteria, in whom a disease-causing TP53 variant has been identified, should be referred to an expert multidisciplinary team for discussion

Recommendation 5

Children with any cancer from southern and south-eastern Brazilian families should be tested for the p.R337H Brazilian founder germline TP53 variant