ORIGINAL PAPER FISH analysis for TET2 deletion in a cohort of 362 Brazilian myeloid malignancies: correlation with karyotype abnormalities Fa ´bio Morato de Oliveira • Carlos Eduardo Miguel • Anto ˆnio Roberto Lucena-Araujo • Ana Silvia Gouve ˆa de Lima • Roberto Passetto Falca ˜o • Eduardo Magalha ˜es Rego Received: 17 December 2012 / Accepted: 22 January 2013 / Published online: 7 February 2013 Ó Springer Science+Business Media New York 2013 Abstract We investigated the prevalence of TET2 deletion by using a new FISH probe in a cohort of 362 Brazilian patients with myeloid neoplasms and their association with cytogenetic information (G-banding analysis). Normal karyotype was observed in 45.8 % of MDS (n = 44), 43.8 % of AML (n = 39) and 46.3 % of MPN (n = 82). Abnor- malities of 4q24 (deletions, translocations or inversions) were associated with another chromosomal abnormality in four patients by G-banding analysis (2 MDS, 1 AML and 1 MPN). Interphase FISH analysis revealed deletion of TET2 in 21 patients (6 patients with abnormal karyotype and in 15 patients with normal karyotype). arrayCGH analysis revealed a cryptic deletion of the region 4q24 in all eight patients selected with myeloid malignancies (3 MDS, 1 AML and 4 MPN). Considering the significantly high cost of determining the mutational status of TET2 in patient samples by using conventional sequencing methods and sometimes the lack of regular use of SNP/aCGH array methodologies, FISH for the detection of TET2 abnormalities may become a potentially useful clinical tool. The search for alterations in TET2 gene may be important for the prediction of prognosis in normal/altered AML patients’ karyotype or in the disease evolution of patients with MNP and MDS. Keywords: TET2 Á MDS Á AML Á MPN Á Cytogenetics Á FISH Á SKY Á arrayCGH Introduction TET2, a putative tumor suppressor gene, located at band 4q24 has been described as an important element in the pathogenesis of myeloid malignancies, including myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN) and acute myeloid leukemia (AML) [1, 2]. Recently, it has been demonstrated that the loss of TET2 is associated with a progressive enlargement of the hema- topoietic stem cell compartment and eventual myelopro- liferation [3]; additionally, the loss of TET2 leads to increased hematopoietic stem cell self-renewal and mye- loid transformation in mice [3–5]. Somatic truncating mutations, including nonsense mutations and small inser- tions/deletions, and missense mutations in TET2, were described in patients with hematological malignancies [5]. These mutations are frequently acquired during progression of MPN or MDS to secondary AML [6–8] and have been associated with low overall survival (OS) rate in patients with AML [9–11]. Considering the significantly high cost of determining the mutational status of TET2 in patient’s samples by using conventional sequencing methods and the lack of regular use of SNP/aCGH array methodologies, FISH for detection of TET2 abnormalities may become a potentially useful clinical tool. The search for alterations in TET2 may be important for prediction of prognosis in patients with AML F. M. de Oliveira (&) Á A. R. Lucena-Araujo Á A. S. G. de Lima Á R. P. Falca ˜o Á E. M. Rego Department of Internal Medicine, Division of Hematology, School of Medicine of Ribeira ˜o Preto, University of Sa ˜o Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeira ˜o Preto, SP, Brazil e-mail: morato.oliveira@yahoo.com.br F. M. de Oliveira Á A. R. Lucena-Araujo Á A. S. G. de Lima Á R. P. Falca ˜o Á E. M. Rego National Institute of Science and Technology in Stem Cell and Cell Therapy, Ribeira ˜o Preto, Brazil C. E. Miguel Hematology Division, Hospital of Base of Sa ˜o Jose ´ do Rio Preto, Sa ˜o Paulo, Brazil 123 Med Oncol (2013) 30:483 DOI 10.1007/s12032-013-0483-1