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@article{1430300, author = {Fontana, M.C. and Marconi, G. and Feenstra, J.D.M. and Fonzi, E. and Papayannidis, C. and di Rora, A.G.L. and Padella, A. and Solli, V. and Franchini, E. and Ottaviani, E. and Ferrari, A. and Baldazzi, C. and Testoni, N. and Iacobucci, I. and Soverini, S. and Haferlach, T. and Guadagnuolo, V. and Semerád, Lukáš and Doubek, Michael and Steurer, M. and Ráčil, Zdeněk and Paolini, S. and Manfrini, M. and Cavo, M. and Simonetti, G. and Kralovics, R. and Martinelli, G.}, article_location = {London}, article_number = {7}, doi = {http://dx.doi.org/10.1038/s41375-018-0035-y}, keywords = {genomic instability; cancer genomes; prostate-cancer; tp53 mutations; classification; prognosis; aml; recommendations; rearrangements; chromosomes}, language = {eng}, issn = {0887-6924}, journal = {Leukemia}, title = {Chromothripsis in acute myeloid leukemia: biological features and impact on survival}, volume = {32}, year = {2018} }
TY - JOUR ID - 1430300 AU - Fontana, M.C. - Marconi, G. - Feenstra, J.D.M. - Fonzi, E. - Papayannidis, C. - di Rora, A.G.L. - Padella, A. - Solli, V. - Franchini, E. - Ottaviani, E. - Ferrari, A. - Baldazzi, C. - Testoni, N. - Iacobucci, I. - Soverini, S. - Haferlach, T. - Guadagnuolo, V. - Semerád, Lukáš - Doubek, Michael - Steurer, M. - Ráčil, Zdeněk - Paolini, S. - Manfrini, M. - Cavo, M. - Simonetti, G. - Kralovics, R. - Martinelli, G. PY - 2018 TI - Chromothripsis in acute myeloid leukemia: biological features and impact on survival JF - Leukemia VL - 32 IS - 7 SP - 1609-1620 EP - 1609-1620 PB - Nature Publishing Group SN - 08876924 KW - genomic instability KW - cancer genomes KW - prostate-cancer KW - tp53 mutations KW - classification KW - prognosis KW - aml KW - recommendations KW - rearrangements KW - chromosomes N2 - Chromothripsis is a one-step genome-shattering catastrophe resulting from disruption of one or few chromosomes in multiple fragments and consequent random rejoining and repair. This study defines incidence of chromothripsis in 395 newly diagnosed adult acute myeloid leukemia (AML) patients from three institutions, its impact on survival and its genomic background. SNP 6.0 or CytoscanHD Array (Affymetrix (R)) were performed on all samples. We detected chromothripsis with a custom algorithm in 26/395 patients. Patients harboring chromothripsis had higher age (p = 0.002), ELN high risk (HR) (p < 0.001), lower white blood cell (WBC) count (p = 0.040), TP53 loss, and/or mutations (p < 0.001) while FLT3 (p = 0.025), and NPM1 (p = 0.032) mutations were mutually exclusive with chromothripsis. Chromothripsis-positive patients showed a worse overall survival (OS) (p < 0.001) compared with HR patients (p = 0.011) and a poor prognosis in a COX-HR optimal regression model. Chromothripsis presented the hallmarks of chromosome instability [i.e., TP53 alteration, 5q deletion, higher mean of copy number alteration (CNA), complex karyotype, alterations in DNA repair, and cell cycle] and focal deletions on chromosomes 4, 7, 12, 16, and 17. CBA. FISH showed that chromothripsis is associated with marker, derivative, and ring chromosomes. In conclusion, chromothripsis frequently occurs in AML (6.6%) and influences patient prognosis and disease biology. ER -
FONTANA, M.C., G. MARCONI, J.D.M. FEENSTRA, E. FONZI, C. PAPAYANNIDIS, A.G.L. DI RORA, A. PADELLA, V. SOLLI, E. FRANCHINI, E. OTTAVIANI, A. FERRARI, C. BALDAZZI, N. TESTONI, I. IACOBUCCI, S. SOVERINI, T. HAFERLACH, V. GUADAGNUOLO, Lukáš SEMERÁD, Michael DOUBEK, M. STEURER, Zdeněk RÁČIL, S. PAOLINI, M. MANFRINI, M. CAVO, G. SIMONETTI, R. KRALOVICS and G. MARTINELLI. Chromothripsis in acute myeloid leukemia: biological features and impact on survival. \textit{Leukemia}. London: Nature Publishing Group, 2018, vol.~32, No~7, p.~1609-1620. ISSN~0887-6924. Available from: https://dx.doi.org/10.1038/s41375-018-0035-y.
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