Multigene amplification and massively parallel sequencing for cancer mutation discovery

Dahl, Fredrik A.; Stenberg, Johan A.; Simon, Fabrice; Welch, Kimo M.; Zhang, Michael; Nilsson, Mats; Bicknell, David; Bodmer, W F; Davis, Ronald W.; Ji, Hanlee P.

doi:10.1073/pnas.0702165104

Cited by 155 publications

(106 citation statements)

References 32 publications

(28 reference statements)

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“…This technique of mutation detection has been validated for a number of genes, including several very large genes such as dystrophin (79 exons) and fibrillin-1 (65 exons) [53,54]. It is anticipated that either massively parallel sequencing of large number of exons or whole genome sequencing techniques will evolve to allow rapid, DNA-based diagnosis in many genetic disorders [55][56][57][58][59]. Until such technology becomes widely accessible and affordable, DHPLC offers a viable strategy for mutation screening.…”

Section: Discussionmentioning

confidence: 99%

Ankyrin‐linked hereditary spherocytosis in an African–American kindred

et al. 2008

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Mutations of ankyrin-1 are the most frequent cause of the inherited hemolytic anemia, hereditary spherocytosis (HS), in people of European ancestry. Ankyrin-1, which provides the primary linkage between the erythrocyte membrane skeleton and the plasma membrane, has numerous isoforms generated by alternative splicing, alternate polyadenylation, use of tissue-specific promoters, and alternate NH 2 or COOH-termini. Mutation detection in erythrocyte membrane protein genes, including ankyrin, has been a challenge, primarily due to the large size of these genes, and the apparent frequent occurrence of HS-associated null alleles. Using denaturing high-performance liquid chromatography (DHPLC), we screened the ankyrin gene of the proband of a large, three generation African-American kindred with ankyrin-deficient HS. DHPLC yielded an abnormal chromatogram for exon 1. Examination of the corresponding exon 1 sequence in genomic DNA from the proband revealed heterozygosity for a mutation of the initiator methionine (ATG to ATA Met 1 Ile). Coupled in vitro transcription/translation studies with rabbit reticulocyte lysates demonstrated that the wild-type ankyrin erythroid cDNA initiates only from the known initiator methionine, indicating that the use of alternate initiator methionine is not a mechanism of isoform diversity in erythroid cells. The mutant ankyrin allele, unlike some initiator methionine mutations that utilize downstream codons for translation initiation, was associated with a null allele. This is the first report describing ankyrin-linked HS in an African-American kindred. Am. J. Hematol. 83:789-794, 2008. V

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Section: Discussionmentioning

confidence: 99%

Ankyrin‐linked hereditary spherocytosis in an African–American kindred

et al. 2008

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“…This application is particularly relevant for ovarian carcinoma because the structural complexity of the genome renders case-by-case evaluation of all chromosome breakpoints near-impossible by traditional cloning methods. Next-generation sequencing will soon supersede the conventional Sanger method as it offers the potential to detect every somatic coding gene mutation in a tumor (Dahl et al, 2007).…”

Section: Future Developmentsmentioning

confidence: 99%

“…Whole genome or targeted resequencing Dahl et al, 2007;Thomas et al, 2006), including multiplexing of samples (Binladen et al, 2007) 400 bp reads. Not validated yet for copy number due to fewer reads per run but base-pair resolution of small alterations and rearrangements.…”

Section: Future Developmentsmentioning

confidence: 99%

Large‐scale genomic analysis of ovarian carcinomas

Gorringe

Campbell

2008

Molecular Oncology

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Epithelial ovarian cancers are typified by frequent genomic aberrations that have been difficult to unravel. Recently, high‐resolution array technologies have provided the first glimpse of the remarkable complexity of these aberrations with some ovarian cancers containing hundreds of copy number breakpoints, micro‐deletions and amplifications. Many of these alterations contain cancer‐related genes suggesting that the majority is disease‐associated and not just the product of random genomic instability. Future developments such as next‐generation sequencing and integrated analysis of data from multiple array platforms on large numbers of samples are poised to revolutionise our understanding of this complex disease.

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“…However, with rapid advances in a new generation of high throughput DNA sequencing technologies (4-6), rapid and low cost sequencing may greatly facilitate mutation recovery from mutagenesis screens. These new sequencing technologies have already proven useful for addressing a wide range of biological questions, from de novo sequencing of microorganisms (7), cancer mutation discovery (8), gene expression profiling (9) to epigenetic regulation (10).…”

mentioning

confidence: 99%

Massively parallel sequencing identifies the gene Megf8 with ENU-induced mutation causing heterotaxy

Zhang

Alpert

Francis

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Forward genetic screens with ENU (N-ethyl-N-nitrosourea) mutagenesis can facilitate gene discovery, but mutation identification is often difficult. We present the first study in which an ENUinduced mutation was identified by massively parallel DNA sequencing. This mutation causes heterotaxy and complex congenital heart defects and was mapped to a 2.2-Mb interval on mouse chromosome 7. Massively parallel sequencing of the entire 2.2-Mb interval identified 2 single-base substitutions, one in an intergenic region and a second causing replacement of a highly conserved cysteine with arginine (C193R) in the gene Megf8. Megf8 is evolutionarily conserved from human to fruit fly, and is observed to be ubiquitously expressed. Morpholino knockdown of Megf8 in zebrafish embryos resulted in a high incidence of heterotaxy, indicating a conserved role in laterality specification. Megf8 C193R mouse mutants show normal breaking of symmetry at the node, but Nodal signaling failed to be propagated to the left lateral plate mesoderm. Videomicroscopy showed nodal cilia motility, which is required for left-right patterning, is unaffected. Although this protein is predicted to have receptor function based on its amino acid sequence, surprisingly confocal imaging showed it is translocated into the nucleus, where it is colocalized with Gfi1b and Baf60C, two proteins involved in chromatin remodeling. Overall, through the recovery of an ENU-induced mutation, we uncovered Megf8 as an essential regulator of left-right patterning.cardiogenesis ͉ left-right ͉ nodal

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Multigene amplification and massively parallel sequencing for cancer mutation discovery

Cited by 155 publications

References 32 publications

Ankyrin‐linked hereditary spherocytosis in an African–American kindred

Ankyrin‐linked hereditary spherocytosis in an African–American kindred

Large‐scale genomic analysis of ovarian carcinomas

Massively parallel sequencing identifies the gene Megf8 with ENU-induced mutation causing heterotaxy

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