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Drosophila larval brain neoplasms present tumour-type dependent genome instability

Fabrizio Rossi, Camille Stephan-Otto Attolini, Jose Luis Mosquera, Cayetano Gonzalez
doi: https://doi.org/10.1101/192492
Fabrizio Rossi
aInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain.
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Camille Stephan-Otto Attolini
aInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain.
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Jose Luis Mosquera
aInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain.
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Cayetano Gonzalez
aInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain.
bCatalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain.
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ABSTRACT

Single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) are found at different rates in human cancer. To determine if these genetic lesions appear in Drosophila tumours we have sequenced the genomes of 17 malignant neoplasms caused by mutations in l(3)mbt, brat, aurA, or lgl. We have found CNVs and SNPs in all the tumours. Tumour-linked CNVs range between 11 and 80 per sample, affecting between 92 and 1546 coding sequences. CNVs are in average less frequent in l(3)mbt than in brat lines. Nearly half of the CNVs fall within the 10 to 100Kb range, all tumour samples contain CNVs larger that 100 Kb and some have CNVs larger than 1Mb. The rates of tumour-linked SNPs change more than 20-fold depending on the tumour type: late stage brat, l(3)mbt, and aurA and lgl lines present median values of SNPs/Mb of exome of 0.16, 0.48, and 3.6, respectively. Higher SNP rates are mostly accounted for by C>A transversions, which likely reflect enhanced oxidative stress conditions in the affected tumours. Both CNVs and SNPs turn over rapidly. We found no evidence for selection of a gene signature affected by CNVs or SNPs in the cohort. Altogether, our results show that the rates of CNVs and SNPs, as well as the distribution of CNV sizes in this cohort of Drosophila tumours are well within the range of those reported for human cancer. Genome instability is therefore inherent to Drosophila malignant neoplastic growth at a variable extent that is tumour type dependent.

AUTHOR SUMMARY Drosophila models of malignant growth can help to understand the molecular mechanisms of malignancy. These models are known to exhibit some of the hallmarks of cancer like sustained growth, immortality, metabolic reprogramming, and others. However, it is currently unclear if these fly models are affected by genome instability, which is another hallmark of many human malignant tumours. To address this issue we have sequenced and analysed the genomes of a cohort of seventeen fly tumour samples. We have found that genome instability is a common trait of Drosophila malignant tumours, which occurs at an extent that is tumour-type dependent, at rates that are similar to those of different human cancers.

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Posted September 22, 2017.
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Drosophila larval brain neoplasms present tumour-type dependent genome instability
Fabrizio Rossi, Camille Stephan-Otto Attolini, Jose Luis Mosquera, Cayetano Gonzalez
bioRxiv 192492; doi: https://doi.org/10.1101/192492
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Drosophila larval brain neoplasms present tumour-type dependent genome instability
Fabrizio Rossi, Camille Stephan-Otto Attolini, Jose Luis Mosquera, Cayetano Gonzalez
bioRxiv 192492; doi: https://doi.org/10.1101/192492

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