Prevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History

Institute of Hospitalization and Scientific Care (IRCCS)

Status: Not yet enrolling

Conditions: Myelofibrosis; Polycythemia Vera; Essential Thrombocythaemia

Treatments: Diagnostic Test: NGS analysis for mutations in genes involved in familial predisposition to hematological malignancies; Diagnostic Test: NGS testing

Study type: Interventional

Funder types: Other

Identifiers

NCT06923670

7221

Details and patient eligibility

About

Philadelphia-negative myeloproliferative neoplasms (MPNs) occur sporadically and are due to somatic mutations in the JAK2 (Janus kinase 2), CALR (calreticulin) and MPL (thrombopoietin receptor) genes. However, data from epidemiological and family studies clearly highlight a heritable component that influences the risk of developing MPN and potentially contributes to the observed phenotypic pleiotropy. Genome-wide association studies in MPN familial clusters have identified a number of germline genetic variants associated with an increased risk of developing MPN. The strongest association discovered so far is the presence of the JAK2 46/1 haplotype and, subsequently, several studies have found additional variants in other genes, particularly in the TERT gene.

The aim of the study would be to investigate the presence of germline mutations in MPN patients selected on the basis of a family history of myeloid neoplasms through the analysis of both already recognized genes and other potentially implicated ones.

Enrollment: 496 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

*Patients >18 years

• Diagnosis of MPN (Essential Thrombocythemia, Polycythemia Vera, Myelofibrosis) confirmed according to ICC 2022 criteria

• Familiarity for myeloid neoplasia: at least one first or second degree relative affected by myeloid neoplasia (probands) OR presence of matching criteria with a proband (controls). Each center will be able to contribute with its own available patients/relatives, providing the clinical-laboratory data required by the study.

  • Signing of informed consent according to ICH/EU/GCP and local national laws (if applicable)

Exclusion criteria

• Patients <18 years Patients with other hematological diagnoses; • Lack of informed consen

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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496 participants in 2 patient groups

Patients with familial history of hematological malignancies

Experimental group

Description:

The investigators will evaluate the presence of mutations in the following genes: ABRAXAS1, ACD, ANKRD26, APC, ATG2B, ATM, BARD1, BMPR1A, BRCA1/2, BRIP1, CDH1, CDKN2A, CEBPA, CHECK2, CSF3R, DDX41, EPCAM, ERCC6L2, ETV6, FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, FANCL, GATA2, GSKIP, MBD4, MECOM, MEN1, MLH1, MLH3, MRE11, MSH2, MSH6, MUTYH, NBN, NF1, NF2, PALB2, PIK3CA, POLD1, POLE, PMS2, PMS2CL, PTEN, PTPN11, RAD50, RAD51C, RAD51D, RET, RTEL1, RUNX1, SAMD9, SAMD9L, SBDS, SRP72, STK11, TERC, TERT, TP53, TSC1, TSC2, VHL, WAS, XRCC2

Treatment:

Diagnostic Test: NGS testing

Diagnostic Test: NGS analysis for mutations in genes involved in familial predisposition to hematological malignancies

Patients without familial history of hematological malignancies

Active Comparator group

Description:

The investigators will evaluate the presence of mutations in the following genes: ABRAXAS1, ACD, ANKRD26, APC, ATG2B, ATM, BARD1, BMPR1A, BRCA1/2, BRIP1, CDH1, CDKN2A, CEBPA, CHECK2, CSF3R, DDX41, EPCAM, ERCC6L2, ETV6, FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, FANCL, GATA2, GSKIP, MBD4, MECOM, MEN1, MLH1, MLH3, MRE11, MSH2, MSH6, MUTYH, NBN, NF1, NF2, PALB2, PIK3CA, POLD1, POLE, PMS2, PMS2CL, PTEN, PTPN11, RAD50, RAD51C, RAD51D, RET, RTEL1, RUNX1, SAMD9, SAMD9L, SBDS, SRP72, STK11, TERC, TERT, TP53, TSC1, TSC2, VHL, WAS, XRCC2

Treatment:

Diagnostic Test: NGS testing

Diagnostic Test: NGS analysis for mutations in genes involved in familial predisposition to hematological malignancies