Chromothripsis is a frequent event and underlies typical genetic changes in early T-cell precursor lymphoblastic leukemia in adults

Autor: Silvia Arniani, Valentina Pierini, Fabrizia Pellanera, Caterina Matteucci, Danika Di Giacomo, Valentina Bardelli, Martina Quintini, Elena Mavridou, Anair Graciela Lema Fernandez, Carlotta Nardelli, Martina Moretti, Paolo Gorello, Barbara Crescenzi, Silvia Romoli, Donatella Beacci, Marco Cerrano, Nicola Fracchiolla, Simona Sica, Fabio Forghieri, Fabio Giglio, Michela Dargenio, Loredana Elia, Roberta La Starza, Cristina Mecucci
Rok vydání: 2022
Předmět:
Zdroj: Leukemia. 36(11)
ISSN: 1476-5551
Popis: Chromothripsis is a mitotic catastrophe that arises from multiple double strand breaks and incorrect re-joining of one or a few chromosomes. We report on incidence, distribution, and features of chromothriptic events in T-cell acute lymphoblastic leukemias (T-ALL). SNP array was performed in 103 T-ALL (39 ETP/near ETP, 59 non-ETP, and 5 with unknown stage of differentiation), including 38 children and 65 adults. Chromothripsis was detected in 11.6% of all T-ALL and occurred only in adult cases with an immature phenotype (12/39 cases; 30%). It affected 1 to 4 chromosomes, and recurrently involved chromosomes 1, 6, 7, and 17. Abnormalities of genes typically associated with T-ALL were found at breakpoints of chromothripsis. In addition, it gave rise to new/rare alterations, such as, the SFPQ::ZFP36L2 fusion, reported in pediatric T-ALL, deletions of putative suppressors, such as IKZF2 and CSMD1, and amplification of the BCL2 gene. Compared to negative cases, chromothripsis positive T-ALL had a significantly higher level of MYCN expression, and a significant downregulation of RGCC, which is typically induced by TP53 in response to DNA damage. Furthermore we identified mutations and/or deletions of DNA repair/genome stability genes in all cases, and an association with NUP214 rearrangements in 33% of cases.
Databáze: OpenAIRE
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