作者
Alberto L′ Abbate, Doron Tolomeo, Ingrid Cifola, Marco Severgnini, Antonella Turchiano, Bartolomeo Augello, Gabriella Squeo, Pietro D′ Addabbo, Debora Traversa, Giulia Daniele, Angelo Lonoce, Mariella Pafundi, Massimo Carella, Orazio Palumbo, Anna Dolnik, Dominique Muehlematter, Jacqueline Schoumans, Nadine Van Roy, Gianluca De Bellis, Giovanni Martinelli, Giuseppe Merla, Lars Bullinger, Claudia Haferlach, Clelia Tiziana Storlazzi
发表日期
2018/10
期刊
Leukemia
卷号
32
期号
10
页码范围
2152-2166
出版商
Nature Publishing Group UK
简介
Double minutes (dmin), homogeneously staining regions, and ring chromosomes are vehicles of gene amplification in cancer. The underlying mechanism leading to their formation as well as their structure and function in acute myeloid leukemia (AML) remain mysterious. We combined a range of high-resolution genomic methods to investigate the architecture and expression pattern of amplicons involving chromosome band 8q24 in 23 cases of AML (AML-amp). This revealed that different MYC-dmin architectures can coexist within the same leukemic cell population, indicating a step-wise evolution rather than a single event origin, such as through chromothripsis. This was supported also by the analysis of the chromothripsis criteria, that poorly matched the model in our samples. Furthermore, we found that dmin could evolve toward ring chromosomes stabilized by neocentromeres. Surprisingly, amplified genes …
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