Correlation of myelodysplastic syndromes with i(17)(q10) and <i><scp>TP</scp>53</i> and <i><scp>SETBP</scp>1</i> mutations

Ademà, Vera; Larráyoz, María José; Calasanz, Marı́a José; Palomo, Laura; Patiño-García, Ana; Agirre, Xabier; Hernández-Rivas, Jesús M.; Lumbreras, Eva; Buño, Ismael; Martínez‐Laperche, Carolina; Mallo, Mar; García, Olga; Álvarez, Sara; Blázquez, Beatriz Segovia; Cervera, José; Luño, Elisa; Valiente, Alberto; Vallespí, Maria Teresa; Arenillas, Leonor; Collado, Rosa; Pérez-Oteyza, J; Solé, Françesc

doi:10.1111/bjh.13355

Cited by 10 publications

(13 citation statements)

References 8 publications

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“…SF3B1 mutations were absent. SETBP1 and TP53 mutations were mutually exclusive as reported by others [ 3 , 9 , 10 ] except in 1 case where TP53 mutation was observed at 5% variant allelic frequency (VAF) in a post allogeneic stem cell transplant setting. In addition to the findings shown in Figure 1 , none of the tested cases had mutations in CEBPA ( n = 15) or MDM4 ( n = 12).…”

Section: Resultssupporting

confidence: 64%

“…We have confirmed that TP53 mutations, even at low allelic frequencies, are exceedingly rare in myeloid neoplasms with isolated i(17q) using next-generation sequencing based mutation analysis. This finding suggests involvement by mechanisms other than TP53 mutation-induced genomic instability [ 1 , 3 , 9 , 10 ]. Alternatively, TP53 dysfunction may be the result of copy number changes or alterations in RNA and protein expression of other molecules of TP53 pathway that have not been explored.…”

Section: Discussionmentioning

confidence: 99%

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Myeloid neoplasms with isolated isochromosome 17q demonstrate a high frequency of mutations in SETBP1, SRSF2, ASXL1 and NRAS

et al. 2016

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Isolated isochromosome 17q, i(17q), accounts for less than 1% of myeloid neoplasms that are commonly classified as myelodysplastic/myeloproliferative neoplasms, acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or myeloproliferative neoplasms (MPN). We have shown previously that these cases have distinctive clinicopathologic features, a poor prognosis and absence of TP53 mutations. However, their molecular mutation profile has not been studied. Here, we explored the mutation profile of 32 cases of myeloid neoplasm with isolated i(17q) that included AML, MDS/MPN, MDS and MPN. In addition to the common i(17q), these neoplasms had frequent mutations in SRSF2 (55%), SETBP1 (59%), ASXL1 (55%), and NRAS (31%); TET2 and TP53 mutations were rare. Eight of 28 patients (29%) showed concurrent mutations in ASXL1, SRSF2, SETBP1 and RAS. There was a significant association between mutations in SETBP1 and RAS (p = 0.003). The mutation pattern was independent of the morphologic diagnosis. Sequential analysis of 5 cases showed evolution from a diploid karyotype to i(17q) and that SRSF2 and ASXL1 mutations precede the detection of i(17q) whereas SETBP1 mutations are associated with i(17q).

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Section: Resultssupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Myeloid neoplasms with isolated isochromosome 17q demonstrate a high frequency of mutations in SETBP1, SRSF2, ASXL1 and NRAS

et al. 2016

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“…Isochromosome 17q (i(17q)) is also associated with SETBP1 mutations (54%) [45,48,57,62]. Especially, TP53 and SETBP1 mutations were completely exclusive in cases with i(17q), suggesting that these two major prognostic events are independently involved in poor outcome in myeloid neoplasms [63]. Such concomitant poor prognostic chromosomal lesions are compatible with worse prognosis in cases with SETBP1 mutations as mentioned below.…”

Section: Coordination With Additional Genetic Eventsmentioning

confidence: 94%

Somatic SETBP1 mutations in myeloid neoplasms

Makishima

2017

Int J Hematol

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“…However, there are cases classified as various MDS, MPN and AML subtypes including acute promyelocytic leukemia and even hypereosinophilic syndrome. 2 , 3 , 5 , 6 , 9 – 11 Another controversial issue is prognosis. Isolated i(17q) has repeatedly been reported to confer a dismal outcome ranging from an mOS of 4.5 6 to up to 14.5 months 3 , 5 in 3 large series.…”

Section: Discussionmentioning

confidence: 99%

Myeloid neoplasms with isolated isochromosome 17q: a yet to be defined entity

Lamprianidou

Kordella

Papoutselis

et al. 2017

Mediterr J Hematol Infect Dis

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Myeloid neoplasms with isolated isochromosome 17q [MN i(17q)] has been described as a distinct entity with poor prognosis. However, literature reports show a considerable clinical and molecular heterogeneity. We describe a 58-year-old male patient who was diagnosed as refractory anemia with multilineage dysplasia and ringed sideroblasts with isolated i(17q). Though he initially responded well to erythropoietin, he gradually progressed to an aggressive form of MDS/MPN refractory to azacytidine and died 29 months after the first diagnosis. Notably, in contrast to disease advancement, his karyotype reverted to normal, whereas his mutational profile remained unchanged. To our knowledge, this is the first report of karyotype normalization during disease progression in patients with MN i(17q). It suggests that the i(17q) anomaly is dispensable for the leukemic transformation and highlighting the underlying clinical and molecular complexity which both has to be resolved before the establishment of MN with isolated i(17q) as a distinct entity.

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Correlation of myelodysplastic syndromes with i(17)(q10) and TP53 and SETBP1 mutations

Cited by 10 publications

References 8 publications

Myeloid neoplasms with isolated isochromosome 17q demonstrate a high frequency of mutations in SETBP1, SRSF2, ASXL1 and NRAS

Myeloid neoplasms with isolated isochromosome 17q demonstrate a high frequency of mutations in SETBP1, SRSF2, ASXL1 and NRAS

Somatic SETBP1 mutations in myeloid neoplasms

Myeloid neoplasms with isolated isochromosome 17q: a yet to be defined entity

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