Multi-Gene Transcriptional Profiling, TP53 Gene Germline Mutation Carrier, TP53 Gene Mutation
Conditions
Brief summary
This is a retrospective, observational, single-center study designed as a cohort analysis. The study population will include consecutive patients referred for genetic counseling and TP53 germline genetic testing between 2004 and 2025 at the Division of Cancer Prevention and Genetics of the IEO. The primary endpoint is to determine the overall detection rate of Pathological Variants (PVs) in the TP53 gene among individuals referred to the institute and the differences between the groups.
Interventions
None listed
Sponsors
European Institute of Oncology
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Have undergone at least one genetic counseling session at the Division of Cancer Prevention and Genetics of the IEO; * Have undergone germline TP53 genetic testing, regardless of the referral criteria for counseling and/or testing or the approach used; * Have provided written informed consent for participation in scientific research.
Exclusion criteria
* Absence of signed informed consent for participation in scientific research.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall detection rate of Pathological Variants (PVs) in the TP53 gene. | Baseline | To determine the overall detection rate of PVs in the TP53 gene among individuals referred to the Division of Cancer Prevention and Genetics at the IEO for TP53 genetic testing. Detection rate calculated as the number of patients with mutation of the TP53 gene divided by the total numer of patients tested. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Detection rate of pathological variants in the TP53 gene across cohort | Baseline | Fisher's exact test or Chi-squared test will be applied, as appropriate, to compare the detection rate of pathological variants in the TP53 gene between different groups. |
| Detection rate of Variant of Uncertain Significance in the TP53 gene. | Baseline | To determine the detection rate of Variant of Uncertain Significance (VUS) in the TP53 gene among all groups. Detection rate calculated as the number of patients with Variant of Uncertain Significance of the TP53 gene divided by the total numer of patients tested. Evaluation for potential reclassification of the detected TP53 VUS according to the 2025 ClinGen TP53 Expert Panel Specifications to the ACMG/AMP Guidelines (v2.3.0) |
| Detection rate of pathological variants and variants of Uncertain Significance in other cancer susceptibility genes. | Baseline | Detection rate calculated as the number of patients with a mutation of gene other than the TP53 gene divided by the total numer of patients tested. |
| Disease Free Survival | 5 years | To compare the Disease Free Survival l of breast cancer patients carrying pathological variants in the TP53 gene with those observed in breast cancer patients tested through Multigene Panel Testing and who did not carry pathological variants or Variants of Uncertain Significance in any of the tested genes. Disease Free Survival will be defined as the time from surgery to invasive loco-regional recurrence, metastasis, other primary non-breast carcinomas, or death from any cause, whichever occurs first. |
| Overall Survival (OS) | 5 years | To compare the Overall Survival of breast cancer patients carrying pathological variants in the TP53 gene with those observed in breast cancer patients tested through Multigene Panel Testing and who did not carry pathological variants or Variants of Uncertain Significance in any of the tested genes. OS will be defined as the time from surgery to death from any cause. |
Countries
Italy
Contacts
CONTACTMariarosaria Calvello, MD
Outcome results
None listed