ETV6: A Candidate Gene for Predisposition to "Blend Pedigrees"? A Case Report from the NEXT-Famly Clinical Trial

Abstract

Background: The identification of germline mutations in familial leukemia predisposition genes by next generation sequencing is of pivotal importance. Lately, some "blend pedigrees" characterized by both solid and hematologic malignancies have been described. Some genes were recognized as related to this double predisposition, while the involvement of others is still a matter of debate. ETV6 was associated with hematologic malignancies, in particular myeloid malignancies, and recently described as mutated also in oncologic patients. No clear evidences in its involvement in blend pedigrees are known. Case Presentation. We present our recent experience in the identification of an ETV6 was associated with hematologic malignancies, in particular myeloid malignancies, and recently described as mutated also in oncologic patients. No clear evidences in its involvement in blend pedigrees are known. ETV6 was associated with hematologic malignancies, in particular myeloid malignancies, and recently described as mutated also in oncologic patients. No clear evidences in its involvement in blend pedigrees are known. ETV6 was associated with hematologic malignancies, in particular myeloid malignancies, and recently described as mutated also in oncologic patients. No clear evidences in its involvement in blend pedigrees are known.

Conclusion: This evidence supports the involvement of ETV6 in the predisposition to both solid and hematologic neoplasia and the importance of the investigation of the noncoding regions of the genes as recently suggested by different expert groups.ETV6 was associated with hematologic malignancies, in particular myeloid malignancies, and recently described as mutated also in oncologic patients. No clear evidences in its involvement in blend pedigrees are known.

Figure 1

Case index pedigree (black arrow indicates the case index; black dot indicates subject presenting mutation; MDS = myelodisplastic syndrome; AML = acute myeloid leukemia).

Figure 2

Electropherogram of the locus containing the mutation revealed by Sanger sequencing. The black arrow indicates the point mutation.

Figure 3

Quantification of ETV6 transcripts by dPCR. The quantification was performed on PBMCs RNA. ETV6 transcript levels were normalized for GAPDH transcript levels and expressed as ratio. Black block: affected relatives; Dark grey block: AML wt-ETV6 cases; Light grey block: healthy subjects. Affected relatives presenting ^∗514C>T variants resulted with ETV6 statistically down regulated in comparison with AML cases presenting wild-type ETV6 (^∗∗∗P=0.0004) and healthy controls (^∗P=0.02). PBMCs = peripheral blood mononuclear cells; AML = acute myeloid leukemia.