Genomic imbalances in benign metastasizing leiomyoma: characterization by conventional karyotypic, fluorescence in situ hybridization, and whole genome SNP array analysis.

Cancer Genet. 2012 May;205(5):249-54

Authors: Bowen JM, Cates JM, Kash S, Itani D, Gonzalez A, Huang D, Oliveira A, Bridge JA

Abstract
Benign metastasizing leiomyoma, a rare condition of controversial origin, is characterized by the occurrence of extrauterine smooth muscle tumors primarily affecting the lungs of women with a history of uterine leiomyomas. Numerous genetic studies of uterine leiomyoma with rearrangements of the HMGA2 and HMGA1 loci defined in prominent subgroups have been conducted. In contrast, cytogenetic and molecular descriptions of benign metastasizing leiomyoma are few, and, in particular, this entity has not been previously subjected to single nucleotide polymorphism (SNP) array analysis. In this study, conventional karyotypic, and/or molecular cytogenetic, and SNP array characterization of a pleuropulmonary benign mestasizing leiomyoma and a synchronous deep soft tissue leiomyoma of the thigh, which arose in a 56-year-old female with a remote history of uterine leiomyomata, revealed rearrangement of the HMGA1 (6p21) locus and nearly identical genomic profiles, including loss of chromosome 7 material in both lesions. These findings suggest that both the deep soft tissue and pleuropulmonary lesions were derived from the same abnormal clone and are genetically related to uterine leiomyomata.

PMID: 22682624 [PubMed - in process]

Development of a dense SNP-based linkage map of an apple rootstock progeny using the Malus Infinium whole genome genotyping array.

BMC Genomics. 2012 May 25;13(1):203

Authors: Antanaviciute L, Fernandez Fernandez F, Jansen J, Banchi E, Evans KM, Viola R, Velasco R, Dunwell JM, Troggio M, Sargent DJ

Abstract
ABSTRACT: BACKGROUND: A whole-genome genotyping array has previously been developed for Malus using SNP data from 28 Malus genotypes. This array offers the prospect of high throughput genotyping and linkage map development for any given Malus progeny. To test the applicability of the array for mapping in diverse Malus genotypes, we applied the array to the construction of a SNP-based linkage map of an apple rootstock progeny. RESULTS: Of the 7,867 Malus SNP markers on the array, 1,823 (23.2%) were heterozygous in one of the two parents of the progeny, 1,007 (12.8%) were heterozygous in both parental genotypes, whilst just 2.8% of the 921 Pyrus SNPs were heterozygous. A linkage map spanning 1,282.2 cM was produced comprising 2,272 SNP markers, 306 SSR markers and the S-locus. The length of the M432 linkage map was increased by 52.7 cM with the addition of the SNP markers, whilst marker density increased from 3.8 cM/marker to 0.5 cM/marker. Just three regions in excess of 10 cM remain where no markers were mapped. We compared the positions of the mapped SNP markers on the M432 map with their predicted positions on the 'Golden Delicious' genome sequence. A total of 311 markers (13.7% of all mapped markers) mapped to positions that conflicted with their predicted positions on the 'Golden Delicious' pseudo-chromosomes, indicating the presence of paralogous genomic regions or mis-assignments of genome sequence contigs during the assembly and anchoring of the genome sequence. CONCLUSIONS: We incorporated data for the 2,272 SNP markers onto the map of the M432 progeny and have presented the most complete and saturated map of the full 17 linkage groups of M. pumila to date. The data were generated rapidly in a high-throughput semi-automated pipeline, permitting significant savings in time and cost over linkage map construction using microsatellites. The application of the array will permit linkage maps to be developed for QTL analyses in a cost-effective manner, and the identification of SNPs that have been assigned erroneous positions on the 'Golden Delicious' reference sequence will assist in the continued improvement of the genome sequence assembly for that variety.

PMID: 22631220 [PubMed - as supplied by publisher]

Detection of novel genomic aberrations in anaplastic astrocytomas by GTG-banding, SKY, locus-specific FISH, and high density SNP-array.

Pathol Res Pract. 2012 May 8;

Authors: Holland H, Ahnert P, Koschny R, Kirsten H, Bauer M, Schober R, Meixensberger J, Fritzsch D, Krupp W

Abstract
Astrocytomas represent the largest and most common subgroup of brain tumors. Anaplastic astrocytoma (WHO grade III) may arise from low-grade diffuse astrocytoma (WHO grade II) or as primary tumors without any precursor lesion. Comprehensive analyses of anaplastic astrocytomas combining both cytogenetic and molecular cytogenetic techniques are rare. Therefore, we analyzed genomic alterations of five anaplastic astrocytomas using high-density single nucleotide polymorphism arrays combined with GTG-banding and FISH-techniques. By cytogenetics, we found 169 structural chromosomal aberrations most frequently involving chromosomes 1, 2, 3, 4, 10, and 12, including two not previously described alterations, a nonreciprocal translocation t(3;11)(p12;q13), and one interstitial chromosomal deletion del(2)(q21q31). Additionally, we detected previously not documented loss of heterozygosity (LOH) without copy number changes in 4/5 anaplastic astrocytomas on chromosome regions 5q11.2, 5q22.1, 6q21, 7q21.11, 7q31.33, 8q11.22, 14q21.1, 17q21.31, and 17q22, suggesting segmental uniparental disomy (UPD), applying high-density single nucleotide polymorphism arrays. UPDs are currently considered to play an important role in the initiation and progression of different malignancies. The significance of previously not described genetic alterations in anaplastic astrocytomas presented here needs to be confirmed in a larger series.

PMID: 22575435 [PubMed - as supplied by publisher]

CalMaTe: A method and software to improve allele-specific copy number of SNP arrays for downstream segmentation.

Bioinformatics. 2012 May 9;

Authors: Ortiz-Estevez M, Aramburu A, Bengtsson H, Neuvial P, Rubio A

Abstract
SUMMARY: CalMaTe calibrates preprocessed allele-specific copy-number estimates (ASCNs) from DNA microarrays by controlling for SNP-specific allelic crosstalk. The resulting ASCNs are on average more accurate, which increases the power of segmentation methods for detecting changes between copy-number states in tumor studies including copy-neutral loss of heterozygosity (LOH). CalMaTe applies to any ASCNs regardless of preprocessing method and microarray technology, e.g. Affymetrix and Illumina. AVAILABILITY: The method is available on CRAN (http://cran.rproject.org/) in the open-source R package calmate, which also includes an add-on to the Aroma Project framework (http://www.aroma-project.org/). CONTACT: arubio@ceit.es.

PMID: 22576175 [PubMed - as supplied by publisher]