My name is Ruth MacKinnon and I’m a researcher in the Victorian Cancer Cytogenetics Service at St Vincent’s Hospital, Melbourne. You can read more on the St Vincent’s Hospital webpage. Cytogenetics is the study of chromosomes. The VCCS is a diagnostic lab which analyses the chromosomes in cancer cells.
ABOUT THIS BLOG
Cancer survival is improving as better treatments become available, but there’s a catch. One of the risks of chemotherapy, radiotherapy, or even some environmental pollutants, is that they can cause another type of cancer, known as therapy-related leukaemia (specifically, therapy-related acute myeloid leukaemia, t-AML), or therapy-related myelodysplastic syndromes (t-MDS). MDS is a blood disease which can develop into leukaemia.
This project aims to help us understand these diseases better by studying their chromosomes.
Leukaemia is a blood cancer. All cancers have the same fundamental cause – something is wrong with the DNA. So sometimes I’ll talk about cancer, sometimes about genetics, and sometimes about my leukaemia project. I’ll probably go off topic too, occasionally.
Coloured pieces of DNA can be made to attach to the chromosome – this shows where that DNA is in the chromosome.
WHAT ARE CHROMOSOMES? WHAT IS DNA?
You’ve probably heard of cancer that runs in families. Most cancers don’t. Even so, cancer is a disease of the genes, it’s just that in most cases the genes first become faulty in the tissue or organ that goes on to become cancerous.
The body is made up of tiny building blocks called cells. Each cell has a set of genes – these are the instructions that control the cell. Think of genes as the words that spell out these instructions. The language they are written in is called DNA. The genes are ordered very precisely into special packages called chromosomes – the chapters.
READING THE BOOK
Sometimes a mistake slips into the genes. A word might be dropped, doubled up, or mis-spelt. These changes can be found relatively easily. In therapy-related leukaemia it can be as if all the pages have fallen out and been stuck back together, with many different sections mixed up. Somewhere among all the corrupted chapters there are a few sentences that tell the cell to become cancerous.
THE PROJECT
My research focuses on changes to chromosomes. Therapy-related leukaemias often have very complicated chromosome changes, but there are patterns, and I look for these. I’ve come up with an explanation for what causes some of these chromosome shuffles. But there’s a lot of work to be done to work out if I’m on the right track, and to work out how to use this information to treat or prevent therapy-related leukaemia.
A lot of the research funding dollars are going to reading the DNA to find errors that cause cancer. But finding and explaining the patterns of these chromosome changes will also provide important clues. We are one of the few labs doing leukaemia chromosome research, especially in Australia.
There are still many riddles to solve in cancer research, and the more angles we attack it from, the better understanding we will have. If we can learn how to use the abnormal chromosome patterns to help understand leukaemia, we will have a strategy that can be used to study other cancers – and many of these have even more mixed up chromosomes.
FURTHER READING
MacKinnon RN, Selan C, Wall M, Baker E, Campbell LJ 2010. The paradox of 20q11.21 amplification in a subset of cases of myeloid malignancy with chromosome 20 deletion. Genes Chromosomes and Cancer 49:998-1013.
MacKinnon RN and Campbell LJ 2011. The role of dicentric chromosome formation and secondary centromere deletion in the evolution of myeloid malignancy. Genetics Research International ID 643628 (open access).
MacKinnon RN, Duivenvoorden HM, Campbell LJ. 2011. Unbalanced translocations of 20q in AML and MDS often involve interstitial rather than terminal deletions of 20q. Cancer Genet. 204:153-61.
Chin LK, Cheah CY, Michael PM, MacKinnon RN, Campbell LJ. 2012. 11q23 rearrangement and duplication of MLLT1-MLL gene fusion in therapy-related acute myeloid leukemia. Leuk Lymphoa. 53:2066-8.
Wall M, Rayeroux KC, MacKinnon RN, Zordan A, Campbell LJ 2012. ETV6 deletion is a common additional abnormality in patients with myelodysplastic syndromes or acute myeloid leukemia and monosomy 7. Haematologica 97:1933-6 (open access).
Chromosomes and Cancer 
[…] About The Leukaemia Project […]
[…] About The Leukaemia Project […]
Some researchers believe that all cancers have the same fundamental cause – something is wrong with the DNA. How Cancer Cells Copy Chromosomes? Are chromosomes linked to cancer? Normal cells become cancer cells because cellular iron overload affects organelles (DNA, chromosomes, etc). Almost any time that scientists see cancer developing, one of the things that has gone wrong early in the process is that the chromosome copying machinery has not worked properly. Cell division is necessary for growing new cells. Before a cell can divide, it makes copies of its chromosomes so that both new cells will have identical genetic material. Because broken DNA is dangerous, a cell has the ability to sense and repair chromosome damage. Some cancer cells have abnormal numbers of chromosomes. Mitotic catastrophe is an event in which a cell is destroyed during mitosis. Mitotic catastrophe is a common phenomenon occurring in cancer cells. The traditional cancer paradigm is one of progressive disease, in which cells gradually accumulate genomic rearrangements and point mutations over years. Scientists have described chromothripsis (a new catastrophic phenomenon): the presence of tens or even hundreds of structural rearrangements, involving spatially localized genomic regions, in primary cancer samples as well as cancer cell lines. Genetic and epigenetic heterogeneity is pervasive in cancer. Chromosome segregation errors can lead to mitotic catastrophes. Iron metabolism is essential for many cellular processes, including DNA synthesis, and many cancer cells exhibit dysregulation in iron metabolism. Such dysregulation creates point mutations, chromosomal aberrations, chromothripsis and mitotic catastrophes. Cancer cells have considerably more iron than normal cells. Primary tumors always develop at body sites of excessive iron deposits. Any cancer is always caused by iron-related genes (genes involved in iron metabolism / hereditary cancers) and iron-related events (when excessive iron accumulates within the cells, tissues, and organs due to various carcinogenic events / sporadic cancers). Direct intratumoral injections of anti-iron agents will beat inoperable tumors and metastases. Accurate clinical iron-deficiency methods will suppress the spread, growth and proliferation of metastatic cancer cells (abnormal iron-rich, iron-saturated, iron-overloaded cells).