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Detection of NOTCH1 mutations in adult T-cell leukemia/lymphoma and peripheral T-cell lymphoma. | LitMetric

We analyzed NOTCH1 gene mutation in 53 adults with mature T-cell leukemia/lymphoma: 21 patients with adult T-cell leukemia (ATL), 25 with T-cell non-Hodgkin's lymphoma (T-NHL), and 7 with T-cell prolymphocytic leukemia. We detected a nonsense mutation, C7249T (resulting in Q2417X, where X is a termination codon) in the PEST domain of NOTCH1 in an ATL patient and detected a 3-bp deletion (positions 7234-7236) that resulted in deletion of a proline codon at codon 2412 in the PEST domain of NOTCH1 in a patient with a T-NHL, peripheral T-cell lymphoma-unspecified (PTCL-u). We also analyzed the expression of NOTCH1 target genes (HES1, CCND1, and MYC), all of which were expressed in the sample of the PTCL-u patient with the NOTCH1 mutation, but found only MYC to be expressed in the sample from the ATL patient. These findings suggest that nonsense mutation in the PEST domain in the ATL case was associated with NOTCH1 signaling through a pathway different from that for T-cell acute lymphoblastic leukemia (T-ALL). Although NOTCH1 mutation occurs infrequently in mature T-cell leukemia/lymphoma, NOTCH1 may be involved in leukemogenesis associated with various forms of T-cell leukemia/lymphoma rather than only with T-ALL.

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http://dx.doi.org/10.1532/IJH97.06165DOI Listing

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