Tumor tissue can acquire somatic alterations known as copy number aberrations (CNAs). The authors devised genoCN, a statistical framework to investigate CNAs (genoCNA) and copy number variations (CNVs) (genoCNV). GenoCNV can also estimate whole genome genotypes. They used data derived from a study of glioblastoma and control tissue using Illumina Human 610-Quad BeadChips. GenoCNA takes into account tissue contamination and can be used to compare normal and tumor tissue from the same individual.

The authors used minimal archived neonatal dried blood spot (DBS) samples to examine whole-genome amplification viability. They used Illumina’s Infinium HD Human610-Quad BeadChips (scanned on the BeadStation 500GX, using BeadStudio software) and tested 24 samples archived for 15-25 years. After protocol optimization they found over 99% call-rates, concluding that whole-genome amplified DNA from these samples can be successful.

The authors explored the relationship between copy number variation and methylation. They investigated malignant pleural mesothelioma tumors and neck squamous cell carcinoma tumors. They used Illumina’s GoldenGate Methylation Assay to interrogate 1505 CpG loci. CNVs were assessed using Affymetrix arrays. Results showed that when there was no or only one allele copies methylation detection results were negative, but with either three, or more than four copies, there was no effects on methylation detection.

Testing negative for suspected 22q11.2 deletion syndrome (DS) may just mean an atypical deletion has not been discovered especially as commercial testing with fluorescence in situ hybridization (FISH) assay only uses N25 or TUPLE1 probes. Here the authors showed that, using Illumina’s HumanCNV370-Quad BeadChips, a female and her male child were found positive for 22q11.2 DS by showing a deletion in another gene—TBX1.

Mental retardation (MR) and multiple congenital abnormalities (MCAs) are though to arise from genetic abnormalities. Using genome-wide analysis of copy number variants (CNVs) of 318 patients with MR with unknown etiology. The authors used the Illumina HumanHap300 and HumanCNV370 BeadChips, along with Affymetrix GeneChips. One CNV in six patients overlapped a known microdeletion/duplication syndrome, another, found in eight patients, was “recently described as a new microdeletion/duplication syndrome.” Over 16% had 63 potentially pathogenic CNVs, and four “showed striking regions of loss of heterozygosity.”

The authors used complete sequencing of the protein-coding genes to find familial pancreatic patients with a germline truncating mutation in PALB2, which they posited as a predisposing factor. The protein product of PALB2 is a binding partner for the most commonly mutated pancreatic cancer gene, BRCA2. Used Infinium II Whole Genome Genotyping Assay, BeadStation software, Genome Analyzer.

The authors used Illumina’s GoldenGate Genotyping Assay to test if viable genetic information could be obtained from archived neonatal dried blood spot (DBS) samples on 3.2mm discs. Of 644 samples, only 7.7% failed genotyping, all of which were from samples collected between 1982-1987; positive results were also affected by filter paper type.

Malignant rhabdoid tumors (RT) may be due to deletions/mutations of INI11 on chromosome 22 leading to loss of this transcriptional control gene. The authors used several methods, including the Illumina 550K BeadChip, to examine INI1 in 51 RT. They localized 97 potentially pathogenic copy number alterations (CNAs) to chromosome 22, including homozygous or heterozygous deletions and copy number neutral LOH, and proposed that it was likely that “INI1 is the primary gene responsible for the development of rhabdoid tumors.”

The rare abnormality of a deletion of the short arm of chromosome 20 was investigated using 21 patients and five relatives. This is associated with JAG1 gene mutations and consequent Alagille syndrome (AGS), which involves various physical problems. The authors used HumanHap550 BeadChips, which have 6,846 SNP probes on 20p. Deletions extended from 20p12.3 to 20p11.21, with 75 known or predicted genes. While 11 patients had AGS only, those with “deletions that extended from the AGS-only region” had additional developmental delay and/or physical abnormalities.