SQSTM1-NUP214: a new gene fusion in adult T-cell acute lymphoblastic leukemia

Gorello, Paolo; Starza, Roberta La; Giacomo, Danika Di; Messina, Monica; Puzzolo, Maria Cristina; Crescenzi, Barbara; Santoro, Alessandra; Chiaretti, Sabina; Mecucci, Cristina

doi:10.3324/haematol.2010.029769

Cited by 31 publications

(44 citation statements)

References 9 publications

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“…[22][23][24][25][26] Mutations of the SQSTM1 gene have been detected in patients with both sporadic and familiar Paget disease of the bone, 27 and protein accumulation can be seen in several different human tumors. 28,29 Oncogenic rearrangements are rare and single-case reports have been described with a nucleoporine gene (SQSTM1-NUP214) in a patient with acute lymphoblastic leukemia 30 and with ALK (SQSTM1-ALK) in a case of ALK-LBCL. 10 However, the true incidence of the SQSTM1 rearrangement in lymphomas might be underestimated if not evaluated by FISH analysis or rearrangement studies; notably conventional cytogenetic abnormalities could be misleading and show a t(2;5) (p23.1;q34.2) chromosomal translocation similar to that of the common NPM-ALK rearrangement, given the close location of NPM and SQSTM1 genes close to the telomere end of chromosome 5.…”

Section: Discussionmentioning

confidence: 98%

STAT3 Pathway Is Activated in ALK-positive Large B-cell Lymphoma Carrying SQSTM1-ALK Rearrangement and Provides a Possible Therapeutic Target

d'Amore

Visco²,

Menin³

et al. 2013

American Journal of Surgical Pathology

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ALK-positive large B-cell lymphomas usually harbor clathrin (CLTC)-ALK rearrangement or, more rarely, nucleophosmin (NPM)-ALK fusion gene. Here we report a large B-cell lymphoma with a peculiar pattern of diffuse and cytoplasmic immunohistochemical staining and carrying sequestosome 1 (SQSTM1)-ALK rearrangement, identified by reverse transcription polymerase chain reaction analysis and Rapid Amplification of cDNA Ends analysis and confirmed by fluorescence in situ hybridization with specific dual-color fusion probes. The gene fusion product and the transcription factor STAT3 are both phosphorylated, and thereby the pathogenetic mechanism of this case shows important analogies with that of NPM-ALK and CLTC-ALK lymphomas, in which STAT3 plays a central role in the lymphomagenesis. Consequently, STAT3 inhibition provides a possible therapeutic target also for lymphomas with SQSTM1-ALK variant translocation.

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Section: Discussionmentioning

confidence: 98%

STAT3 Pathway Is Activated in ALK-positive Large B-cell Lymphoma Carrying SQSTM1-ALK Rearrangement and Provides a Possible Therapeutic Target

d'Amore

Visco²,

Menin³

et al. 2013

American Journal of Surgical Pathology

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“…Mutations of these genes have been reported in haematological malignancies, e.g. SQSTM1-NUP214 gene fusion in cases of T-cell acute lymphoblastic leukaemias (ALL), but not in AML (Gorello et al, 2010). In addition, our study identified potential novel coding mutations in MAP3K1 ( MEKK ), MAP3K6 ( MEKK6 ), EP300 ( p300 ), and WDR90 (Table SI).…”

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confidence: 99%

Genomics of primary chemoresistance and remission induction failure in paediatric and adult acute myeloid leukaemia

et al. 2016

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Cure rates of children and adults with acute myeloid leukaemia (AML) remain unsatisfactory partly due to chemotherapy resistance. We investigated the genetic basis of AML in 107 primary cases by sequencing 670 genes mutated in haematological malignancies. SETBP1, ASXL1 and RELN mutations were significantly associated with primary chemoresistance. We identified genomic alterations not previously described in AML, together with distinct genes that were significantly overexpressed in therapy-resistant AML. Defined gene mutations were sufficient to explain primary induction failure in only a minority of cases. Thus, additional genetic or molecular mechanisms must cause primary chemoresistance in paediatric and adult AML.

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“…We identified several novel cryptic gene rearrangements including intergenic deletions involving NOTCH1/EDF1 and GATA2/DNAJB8, as well as translocations leading to the rearrangements of SQSTM1-NUP214 and IGH-BCL2. Mutations of these genes have been reported in hematologic malignancies, for example the SQSTM1-NUP214 gene fusion in cases of T-cell acute lymphoblastic leukemias (ALL), but not in AML 16 .…”

Section: Resultsmentioning

confidence: 99%

Genomics of primary chemoresistance and remission induction failure in pediatric and adult acute myeloid leukemia

Brown¹,

Cifani²,

Drill³

et al. 2016

Preprint

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2 Key Points• Targeted gene sequencing of 670 genes in adult and pediatric AML • Profiling of 107 primary AML samples identifies new genomic alterations for primary chemoresistance AbstractDespite intense efforts, the cure rates of children and adults with AML remain unsatisfactory in large part due to resistance to chemotherapy. Whilst cytogenetic risk stratification proved valuable in identifying causes of therapy failure and disease relapse, cytogenetically normal AML remains the most prevalent disease type, with significant heterogeneity of clinical outcomes, including primary chemoresistance. Using targeted sequencing of 670 genes recurrently mutated in hematologic malignancies, we investigated the genetic basis of primary chemotherapy resistance and remission induction failure of 107 primary cases obtained at diagnosis from children and adults with cytogenetically normal AML. Comparative analysis revealed mutations of SETBP1, ASXL1 and RELN to be significantly enriched at diagnosis in primary induction failure as compared to remission cases. In addition, this analysis revealed novel genomic alterations not previously described in AML, as well as distinct genes that are significantly overexpressed in therapy resistant AML. However, identified gene mutations were sufficient to explain only a minority of cases of primary induction failure. Thus, additional genetic or molecular mechanisms must cause primary chemoresistance in pediatric and adult acute myeloid leukemias.

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SQSTM1-NUP214: a new gene fusion in adult T-cell acute lymphoblastic leukemia

Abstract: Letters to the Editor © F e r r a t a S t o r t i F o u n d a t i o n

Cited by 31 publications

References 9 publications

STAT3 Pathway Is Activated in ALK-positive Large B-cell Lymphoma Carrying SQSTM1-ALK Rearrangement and Provides a Possible Therapeutic Target

STAT3 Pathway Is Activated in ALK-positive Large B-cell Lymphoma Carrying SQSTM1-ALK Rearrangement and Provides a Possible Therapeutic Target

Genomics of primary chemoresistance and remission induction failure in paediatric and adult acute myeloid leukaemia

Genomics of primary chemoresistance and remission induction failure in pediatric and adult acute myeloid leukemia

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