MYC-containing amplicons in acute myeloid leukemia: genomic structures, evolution, and transcriptional consequences

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 MartinelliGiuseppe Merla, Lars Bullinger, Claudia Haferlach, Clelia Tiziana Storlazzi

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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 (mainly PVT1) frequently participated in fusion transcripts lacking a corresponding DNA template. We also detected a significant overexpression of the circular RNA of PVT1 (circPVT1) in AML-amp cases versus AML with a normal karyotype. Our results show that 8q24 amplicons in AML are surprisingly plastic DNA structures with an unexpected association to novel fusion transcripts and circular RNAs.

Original languageEnglish
Pages (from-to)1-15
Number of pages15
JournalLeukemia
DOIs
Publication statusAccepted/In press - Feb 22 2018

Fingerprint

Acute Myeloid Leukemia
Ring Chromosomes
Gene Amplification
DNA
Karyotype
Plastics
Chromosomes
Staining and Labeling
Population
Genes
Neoplasms

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

L´Abbate, A., Tolomeo, D., Cifola, I., Severgnini, M., Turchiano, A., Augello, B., ... Storlazzi, C. T. (Accepted/In press). MYC-containing amplicons in acute myeloid leukemia: genomic structures, evolution, and transcriptional consequences. Leukemia, 1-15. https://doi.org/10.1038/s41375-018-0033-0

MYC-containing amplicons in acute myeloid leukemia : genomic structures, evolution, and transcriptional consequences. / L´Abbate, Alberto; Tolomeo, Doron; Cifola, Ingrid; Severgnini, Marco; Turchiano, Antonella; Augello, Bartolomeo; Squeo, Gabriella; D´Addabbo, Pietro; Traversa, Debora; Daniele, Giulia; Lonoce, Angelo; Pafundi, Mariella; Carella, Massimo; Palumbo, Orazio; Dolnik, Anna; Muehlematter, Dominique; Schoumans, Jacqueline; van Roy, Nadine; de Bellis, Gianluca; Martinelli, Giovanni; Merla, Giuseppe; Bullinger, Lars; Haferlach, Claudia; Storlazzi, Clelia Tiziana.

In: Leukemia, 22.02.2018, p. 1-15.

Research output: Contribution to journalArticle

L´Abbate, A, Tolomeo, D, Cifola, I, Severgnini, M, Turchiano, A, Augello, B, Squeo, G, D´Addabbo, P, Traversa, D, Daniele, G, Lonoce, A, Pafundi, M, Carella, M, Palumbo, O, Dolnik, A, Muehlematter, D, Schoumans, J, van Roy, N, de Bellis, G, Martinelli, G, Merla, G, Bullinger, L, Haferlach, C & Storlazzi, CT 2018, 'MYC-containing amplicons in acute myeloid leukemia: genomic structures, evolution, and transcriptional consequences', Leukemia, pp. 1-15. https://doi.org/10.1038/s41375-018-0033-0
L´Abbate, Alberto ; Tolomeo, Doron ; Cifola, Ingrid ; Severgnini, Marco ; Turchiano, Antonella ; Augello, Bartolomeo ; Squeo, Gabriella ; D´Addabbo, Pietro ; Traversa, Debora ; Daniele, Giulia ; Lonoce, Angelo ; Pafundi, Mariella ; Carella, Massimo ; Palumbo, Orazio ; Dolnik, Anna ; Muehlematter, Dominique ; Schoumans, Jacqueline ; van Roy, Nadine ; de Bellis, Gianluca ; Martinelli, Giovanni ; Merla, Giuseppe ; Bullinger, Lars ; Haferlach, Claudia ; Storlazzi, Clelia Tiziana. / MYC-containing amplicons in acute myeloid leukemia : genomic structures, evolution, and transcriptional consequences. In: Leukemia. 2018 ; pp. 1-15.
@article{15895e75b67e401c9a70110641e26f66,
title = "MYC-containing amplicons in acute myeloid leukemia: genomic structures, evolution, and transcriptional consequences",
abstract = "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 (mainly PVT1) frequently participated in fusion transcripts lacking a corresponding DNA template. We also detected a significant overexpression of the circular RNA of PVT1 (circPVT1) in AML-amp cases versus AML with a normal karyotype. Our results show that 8q24 amplicons in AML are surprisingly plastic DNA structures with an unexpected association to novel fusion transcripts and circular RNAs.",
author = "Alberto L´Abbate and Doron Tolomeo and Ingrid Cifola and Marco Severgnini and Antonella Turchiano and Bartolomeo Augello and Gabriella Squeo and Pietro D´Addabbo and Debora Traversa and Giulia Daniele and Angelo Lonoce and Mariella Pafundi and Massimo Carella and Orazio Palumbo and Anna Dolnik and Dominique Muehlematter and Jacqueline Schoumans and {van Roy}, Nadine and {de Bellis}, Gianluca and Giovanni Martinelli and Giuseppe Merla and Lars Bullinger and Claudia Haferlach and Storlazzi, {Clelia Tiziana}",
year = "2018",
month = "2",
day = "22",
doi = "10.1038/s41375-018-0033-0",
language = "English",
pages = "1--15",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - MYC-containing amplicons in acute myeloid leukemia

T2 - genomic structures, evolution, and transcriptional consequences

AU - L´Abbate, Alberto

AU - Tolomeo, Doron

AU - Cifola, Ingrid

AU - Severgnini, Marco

AU - Turchiano, Antonella

AU - Augello, Bartolomeo

AU - Squeo, Gabriella

AU - D´Addabbo, Pietro

AU - Traversa, Debora

AU - Daniele, Giulia

AU - Lonoce, Angelo

AU - Pafundi, Mariella

AU - Carella, Massimo

AU - Palumbo, Orazio

AU - Dolnik, Anna

AU - Muehlematter, Dominique

AU - Schoumans, Jacqueline

AU - van Roy, Nadine

AU - de Bellis, Gianluca

AU - Martinelli, Giovanni

AU - Merla, Giuseppe

AU - Bullinger, Lars

AU - Haferlach, Claudia

AU - Storlazzi, Clelia Tiziana

PY - 2018/2/22

Y1 - 2018/2/22

N2 - 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 (mainly PVT1) frequently participated in fusion transcripts lacking a corresponding DNA template. We also detected a significant overexpression of the circular RNA of PVT1 (circPVT1) in AML-amp cases versus AML with a normal karyotype. Our results show that 8q24 amplicons in AML are surprisingly plastic DNA structures with an unexpected association to novel fusion transcripts and circular RNAs.

AB - 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 (mainly PVT1) frequently participated in fusion transcripts lacking a corresponding DNA template. We also detected a significant overexpression of the circular RNA of PVT1 (circPVT1) in AML-amp cases versus AML with a normal karyotype. Our results show that 8q24 amplicons in AML are surprisingly plastic DNA structures with an unexpected association to novel fusion transcripts and circular RNAs.

UR - http://www.scopus.com/inward/record.url?scp=85042218005&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85042218005&partnerID=8YFLogxK

U2 - 10.1038/s41375-018-0033-0

DO - 10.1038/s41375-018-0033-0

M3 - Article

AN - SCOPUS:85042218005

SP - 1

EP - 15

JO - Leukemia

JF - Leukemia

SN - 0887-6924

ER -