- About
- Strategic Plan
- Structure
- Governance
- Scientific divisions
- ACRF Cancer Biology and Stem Cells
- ACRF Chemical Biology
- Advanced Technology and Biology
- Bioinformatics
- Blood Cells and Blood Cancer
- Clinical Translation
- Epigenetics and Development
- Immunology
- Infectious Diseases and Immune Defence
- Inflammation
- Personalised Oncology
- Population Health and Immunity
- Structural Biology
- Ubiquitin Signalling
- Laboratory operations
- Funding
- Annual reports
- Human research ethics
- Scientific integrity
- Institute life
- Career opportunities
- Business Development
- Collaborators
- Suppliers
- Publications repository
- Awards
- Discoveries
- Centenary 2015
- History
- Contact us
- Research
- Diseases
- Cancer
- Development and ageing
- Immune health and infection
- Research fields
- Research technologies
- Research centres
- People
- Alistair Brown
- Anne-Laure Puaux
- Assoc Prof Joanna Groom
- Associate Profesor Ian Majewski
- Associate Professor Aaron Jex
- Associate Professor Alyssa Barry
- Associate Professor Andrew Webb
- Associate Professor Chris Tonkin
- Associate Professor Daniel Gray
- Associate Professor Diana Hansen
- Associate Professor Edwin Hawkins
- Associate Professor Ethan Goddard-Borger
- Associate Professor Gemma Kelly
- Associate Professor Grant Dewson
- Associate Professor Isabelle Lucet
- Associate Professor James Vince
- Associate Professor Jason Tye-Din
- Associate Professor Jeanne Tie
- Associate Professor Jeff Babon
- Associate Professor Joan Heath
- Associate Professor John Wentworth
- Associate Professor Justin Boddey
- Associate Professor Kate Sutherland
- Associate Professor Marie-Liesse Asselin-Labat
- Associate Professor Matthew Ritchie
- Associate Professor Melissa Call
- Associate Professor Melissa Davis
- Associate Professor Misty Jenkins
- Associate Professor Nawaf Yassi
- Associate Professor Oliver Sieber
- Associate Professor Peter Czabotar
- Associate Professor Rachel Wong
- Associate Professor Rhys Allan
- Associate Professor Rosie Watson
- Associate Professor Ruth Kluck
- Associate Professor Sandra Nicholson
- Associate Professor Seth Masters
- Associate Professor Sumitra Ananda
- Associate Professor Tim Thomas
- Associate Professor Tracy Putoczki
- Chela Niall
- Deborah Carr
- Dr Alisa Glukhova
- Dr Anna Coussens
- Dr Ashley Ng
- Dr Belinda Phipson
- Dr Ben Tran
- Dr Bernhard Lechtenberg
- Dr Brad Sleebs
- Dr Drew Berry
- Dr Gwo Yaw Ho
- Dr Hamish King
- Dr Hui-Li Wong
- Dr Jacqui Gulbis
- Dr Kelly Rogers
- Dr Lucy Gately
- Dr Margaret Lee
- Dr Mary Ann Anderson
- Dr Maryam Rashidi
- Dr Matthew Call
- Dr Nadia Davidson
- Dr Philippe Bouillet
- Dr Rebecca Feltham
- Dr Rory Bowden
- Dr Samir Taoudi
- Dr Shabih Shakeel
- Dr Shalin Naik
- Dr Sheau Wen Lok
- Dr Stephin Vervoort
- Dr Yunshun Chen
- Guillaume Lessene
- Helene Martin
- Joh Kirby
- Kaye Wycherley
- Keely Bumsted O'Brien
- Mr Mark Eaton
- Mr Simon Monard
- Mr Steve Droste
- Ms Carolyn MacDonald
- Professor Alan Cowman
- Professor Andreas Strasser
- Professor Andrew Lew
- Professor Andrew Roberts
- Professor Anne Voss
- Professor Clare Scott
- Professor David Huang
- Professor David Komander
- Professor David Vaux
- Professor Doug Hilton
- Professor Geoff Lindeman
- Professor Gordon Smyth
- Professor Ian Wicks
- Professor Ivo Mueller
- Professor James McCarthy
- Professor James Murphy
- Professor Jane Visvader
- Professor Jerry Adams
- Professor John Silke
- Professor Ken Shortman
- Professor Leanne Robinson
- Professor Leonard C Harrison
- Professor Lynn Corcoran
- Professor Marc Pellegrini
- Professor Marco Herold
- Professor Marnie Blewitt
- Professor Melanie Bahlo
- Professor Mike Lawrence
- Professor Nicos Nicola
- Professor Peter Colman
- Professor Peter Gibbs
- Professor Phil Hodgkin
- Professor Sant-Rayn Pasricha
- Professor Stephen Nutt
- Professor Suzanne Cory
- Professor Terry Speed
- Professor Tony Papenfuss
- Professor Wai-Hong Tham
- Professor Warren Alexander
- Diseases
- Education
- PhD
- Honours
- Masters
- Clinician-scientist training
- Undergraduate
- Student research projects
- A new regulator of 'stemness' to create dendritic cell factories for immunotherapy
- Advanced imaging interrogation of pathogen induced NETosis
- Cancer driver deserts
- Cryo-electron microscopy of Wnt signalling complexes
- Deciphering the heterogeneity of breast cancer at the epigenetic and genetic levels
- Developing drugs to block malaria transmission
- Developing new computational tools for CRISPR genomics to advance cancer research
- Developing novel antibody-based methods for regulating apoptotic cell death
- Discovering novel paradigms to cure viral and bacterial infections
- Discovery and targeting of novel regulators of transcription
- Dissecting host cell invasion by the diarrhoeal pathogen Cryptosporidium
- Do membrane forces govern assembly of the deadly apoptotic pore?
- Doublecortin-like kinases, drug targets in cancer and neurological disorders
- E3 ubiquitin ligases in neurodegeneration, autoinflammation and cancer
- Engineering improved CAR-T cell therapies
- Epigenetic biomarkers of tuberculosis infection
- Exploiting cell death pathways in regulatory T cells for cancer immunotherapy
- Finding treatments for chromatin disorders of intellectual disability
- Functional epigenomics in human B cells
- Genomic rearrangement detection with third generation sequencing technology
- How does DNA damage shape disease susceptibility over a lifetime?
- How does DNA hypermutation shape the development of solid tumours?
- How platelets prevent neonatal stroke
- Human lung protective immunity to tuberculosis
- Interaction with Toxoplasma parasites and the brain
- Interactions between tumour cells and their microenvironment in non-small cell lung cancer
- Investigating the role of dysregulated Tom40 in neurodegeneration
- Investigating the role of mutant p53 in cancer
- Lupus: proteasome inhibitors and inflammation
- Machine learning methods for somatic genome rearrangement detection
- Malaria: going bananas for sex
- Measurements of malaria parasite and erythrocyte membrane interactions using cutting-edge microscopy
- Measuring susceptibility of cancer cells to BH3-mimetics
- Minimising rheumatic adverse events of checkpoint inhibitor cancer therapy
- Mutational signatures of structural variation
- Naturally acquired immune response to malaria parasites
- Predicting the effect of non-coding structural variants in cancer
- Revealing the epigenetic origins of immune disease
- Reversing antimalarial resistance in human malaria parasites
- Structural and functional analysis of DNA repair complexes
- Targeting human infective coronaviruses using alpaca antibodies
- Towards targeting altered glial biology in high-grade brain cancers
- Uncovering the real impact of persistent malaria infections
- Understanding Plasmodium falciparum invasion of red blood cells
- Understanding how malaria parasites sabotage acquisition of immunity
- Understanding malaria infection dynamics
- Understanding the mechanism of type I cytokine receptor activation
- Unveiling the heterogeneity of small cell lung cancer
- Using alpaca antibodies to understand malaria invasion and transmission
- Using combination immunotherapy to tackle heterogeneous brain tumours
- Using intravital microscopy for immunotherapy against brain tumours
- Using nanobodies to cross the blood brain barrier for drug delivery
- Using structural biology to understand programmed cell death
- School resources
- Frequently asked questions
- Student profiles
- Abebe Fola
- Andrew Baldi
- Anna Gabrielyan
- Bridget Dorizzi
- Casey Ah-Cann
- Catia Pierotti
- Emma Nolan
- Huon Wong
- Jing Deng
- Joy Liu
- Kaiseal Sarson-Lawrence
- Komal Patel
- Lilly Backshell
- Megan Kent
- Naomi Jones
- Rebecca Delconte
- Roberto Bonelli
- Rune Larsen
- Runyu Mao
- Sarah Garner
- Simona Seizova
- Wayne Cawthorne
- Wil Lehmann
- Miles Horton
- Alexandra Gurzau
- Student achievements
- Student association
- Learning Hub
- News
- Donate
- Online donation
- Ways to support
- Support outcomes
- Supporter stories
- Rotarians against breast cancer
- A partnership to improve treatments for cancer patients
- 20 years of cancer research support from the Helpman family
- A generous gift from a cancer survivor
- A gift to support excellence in Australian medical research
- An enduring friendship
- Anonymous donor helps bridge the 'valley of death'
- Renewed support for HIV eradication project
- Searching for solutions to muscular dystrophy
- Supporting research into better treatments for colon cancer
- Taking a single cell focus with the DROP-seq
- WEHI.TV
Scientists solve mystery of ‘Frankenstein’ DNA
11 November 2014
from the Peter MacCallum Cancer Centre and
Garvan Institute of Medical Research have
discovered how giant chromosome found in some
cancers form.
Australian researchers have uncovered how the massive DNA molecules that appear in some tumours are formed like Frankenstein’s monster, stitched together from other parts of the genome. This solves a decades-old mystery and explains how these tumours ensure their own survival.
The discovery also identified a potential drug target for treating cancers that are well known to harbour these molecules, dubbed ‘neochromosomes’. Neochromosomes are giant, extra chromosomes found in up to three per cent of all cancers, most commonly in liposarcomas (tumours of fat tissue), sarcomas (soft tissue tumours) and some brain and blood cancers.
Research published today in the journal Cancer Cell, showed that spontaneous and catastrophic chromosomal ‘explosions’ trigger formation of neochromosomes. The shattered relics reassemble haphazardly, followed by a genetic frenzy of amplification and deletion. Genes known to be important for cancer development are massively amplified, assuring the cancer’s survival.
The discovery was a collaborative venture between the Peter MacCallum Cancer Centre, Walter and Eliza Hall Institute of Medical Research and Garvan Institute of Medical Research.
Chromosomes are the packages of genetic information found in all cells of the body. Each normal cell has 23 pairs. Neochromosomes were first identified in the 1950s, but their development was a mystery until now. They are large (often many times the size of the largest normal chromosome), and harbour many extra copies of ‘oncogenes’ (altered genes known to drive cancer development).
The researchers, led by Professor David Thomas and Associate Professor Tony Papenfuss, mapped the neochromosomes from liposarcomas, using next-generation DNA sequencing. The team then used mathematical modelling to reconstruct the sequence of events that caused the neochromosome to form, deducing that only chromosomal shattering could be to blame.
Associate Professor Papenfuss, from the Walter and Eliza Hall Institute and Peter MacCallum Cancer Centre, said the research was like archaeology, sifting through the ruins of a past catastrophic event to understand the present. “We showed that chromosome 12 shatters and its remnants form a ring of DNA in a haphazard fashion,” he said. “As cells divide, and the circular chromosomes get copied and pulled into different cells, a constant abnormal morphing takes place. Small circles gradually become giant circles, progressively amplifying certain genes in what appears to be a selective process. The growing giant also sucks in DNA from all parts of the genome. At a certain point, the circle stops growing and becomes linear. By the time we look at tumour cells through the microscope, we see giant linear chromosomes.”
Professor Thomas, Director of The Kinghorn Cancer Centre at the Garvan Institute, said the extent of the genetic rearrangement was truly astonishing. “These cancers manipulate the normal replication process in an ingenious way, creating a monster that can selectively steal and amplify the genes it needs to grow and survive,” he said. “In some liposarcoma cell lines, DNA from every chromosome in the cell was found in the neochromosome, with between 60 and 100 copies of key oncogenes. Patient tumours also exhibited similar gene rearrangement.”
The study also identified a potential therapeutic target to explore for treating liposarcomas, Professor Thomas said. “When the key oncogenes that were massively amplified in the cancer cells were blocked, the cancer cells died,” he said.
Associate Professor Papenfuss and Professor Thomas led the research team, with Dr Dale Garsed from the Peter MacCallum Cancer Centre, Dr Owen Marshall from the Murdoch Children’s Research Institute and Dr Vincent Corbin from the Walter and Eliza Hall Institute. The research was supported by the National Health and Medical Research Council and Victorian Government. The Walter and Eliza Hall Institute of Medical Research and the Peter MacCallum Cancer Centre are partners in the Victorian Comprehensive Cancer Centre.
Read the paper 'The Architecture and Evolution of Cancer Neochromosomes'.
Further information:
Alan Gill
Science Communications Officer
P: +61 3 9345 2719
E: gill.a@wehi.edu.au