genomic_instability [Neurosurgery Wiki]

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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.
)).

[[Meningioma]]s with mutant [[NF2]] and/or [[chromosome 22]] loss were more likely to be atypical, showing [[genomic instability]], and localizing to the cerebral and cerebellar hemispheres
((Clark VE, Erson-Omay EZ, Serin A, Yin J, Cotney J, Ozduman K, Avşar T, Li J,
Murray PB, Henegariu O, Yilmaz S, Günel JM, Carrión-Grant G, Yilmaz B, Grady C,
Tanrikulu B, Bakircioğlu M, Kaymakçalan H, Caglayan AO, Sencar L, Ceyhun E, Atik 
AF, Bayri Y, Bai H, Kolb LE, Hebert RM, Omay SB, Mishra-Gorur K, Choi M, Overton 
JD, Holland EC, Mane S, State MW, Bilgüvar K, Baehring JM, Gutin PH, Piepmeier
JM, Vortmeyer A, Brennan CW, Pamir MN, Kiliç T, Lifton RP, Noonan JP, Yasuno K,
Günel M. Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7,
KLF4, AKT1, and SMO. Science. 2013 Mar 1;339(6123):1077-80. doi:
10.1126/science.1233009. PubMed PMID: 23348505; PubMed Central PMCID: PMC4808587.)).