[[Genomic instability]] is a frequently occurring feature of [[cancer]] that involves large-scale structural alterations. These somatic changes in [[chromosome]] structure include duplication of entire chromosome arms and [[aneuploidy]] where chromosomes are duplicated beyond normal diploid content. However, the accurate determination of aneuploidy events in cancer genomes is a challenge. Advances in sequencing technology allow the characterization of haplotypes that extend megabases along the human genome using high molecular weight (HMW) DNA. 

Bell et al. employed a library preparation method in which sequence reads have barcodes linked to single HMW DNA molecules. Barcode-linked reads are used to generate extended haplotypes on the order of megabases. We developed a method that leverages haplotypes to identify chromosomal segmental alterations in cancer and uses this information to join haplotypes together, thus extending the range of phased variants. With this approach, we identified mega-haplotypes that encompass entire chromosome arms. We characterized the chromosomal arm changes and aneuploidy events in a manner that offers similar information as a traditional karyotype but with the benefit of DNA sequence resolution
((Bell JM, Lau BT, Greer SU, Wood-Bouwens C, Xia LC, Connolly ID, Gephart MH, Ji
HP. Chromosome-scale mega-haplotypes enable digital karyotyping of cancer
aneuploidy. Nucleic Acids Res. 2017 Aug 16. doi: 10.1093/nar/gkx712. [Epub ahead 
of print] PubMed PMID: 28977555.
)).
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Acquired [[aneuploidy]] was frequently detected in [[recurrent]] [[glioma]]s and was characterized by [[IDH mutation]] but without  [[1p/19q co-deletion]], and further converged with acquired alterations in the [[cell cycle]] and poor [[outcome]]s. The clonal architecture of each tumor remained similar over time, but the presence of subclonal selection was associated with decreased [[survival]]. Finally, there were no differences in the levels of immunoediting between initial and recurrent gliomas. Collectively, the results suggest that the strongest selective pressures occur during early [[glioma development]] and that current therapies shape this evolution in a largely stochastic manner
((Barthel FP, Johnson KC, Varn FS, Moskalik AD, Tanner G, Kocakavuk E, Anderson 
KJ, Abiola O, Aldape K, Alfaro KD, Alpar D, Amin SB, Ashley DM, Bandopadhayay P, 
Barnholtz-Sloan JS, Beroukhim R, Bock C, Brastianos PK, Brat DJ, Brodbelt AR,
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Malta TM, Mazor T, McDonald KL, Molinaro AM, Nam DH, Nayyar N, Ng HK, Ngan CY,
Niclou SP, Niers JM, Noushmehr H, Noorbakhsh J, Ormond DR, Park CK, Poisson LM,
Rabadan R, Radlwimmer B, Rao G, Reifenberger G, Sa JK, Schuster M, Shaw BL, Short
SC, Smitt PAS, Sloan AE, Smits M, Suzuki H, Tabatabai G, Van Meir EG, Watts C,
Weller M, Wesseling P, Westerman BA, Widhalm G, Woehrer A, Yung WKA, Zadeh G,
Huse JT, De Groot JF, Stead LF, Verhaak RGW; GLASS Consortium. Longitudinal
molecular trajectories of diffuse glioma in adults. Nature. 2019 Nov 20. doi:
10.1038/s41586-019-1775-1. [Epub ahead of print] PubMed PMID: 31748746.
)).