The National Cancer Institute (NCI), Genetic Epidemiology Branch (GEB), plans to procure on a sole source sample labeling, quality control, CGH hybridization, array scans, data extraction, and segmentation analysis on DNA samples extracted from blood of subjects in melanoma-prone families from Roche NimbleGen, Inc.; 1 Science Court; Madison, WI 53711.

The services herein are being procured in accordance with the simplified acquisition procedures authorized by FAR Part 13.106-1 (b) (1). The North American Industry Classification System Code is 541711 the business size standard is 500 employees.

The GEB investigators have recruited and actively evaluated over 75 melanoma-prone families since the mid 70s. Among these families, 23 and 2 segregate CDKN2A and CDK4 mutations, respectively. Four other families were linked to the 9p21 region but did not have CDKN2A mutations, suggesting that other CDKN2A-inactivating mechanisms or additional genes on 9p21 might be responsible for CMM predisposition in these families. The rest of our families do not carry mutations of the known genes. Based on data from a natural history study of our melanoma families, mutation negative families did not differ significantly from families segregating CDKN2A and CDK4 in clinical and phenotypic characteristics, such as number of primary melanomas and dysplastic nevi (DN) status. Compared to sporadic melanoma cases, melanoma cases in our mutation negative families have earlier age-onset and higher prevalence of multiple melanomas and DN, suggesting the existence of genetic predisposition. However, since most of these families we have evaluated only have 2 to 3 living melanoma cases, linkage analysis may lack power in identifying susceptibility genes particularly under the situation of genetic heterogeneity.

The objective of this procurement is to perform CGH on whole-genome arrays to identify copy number changes that segregate with disease traits in CMM families. Specifically, genomic DNA from blood samples of 80 subjects from 27 families without known mutations will be analyzed for arrayCGH to identify disease-related CNVs.

The results will be useful to identify additional genes and novel mechanisms that are associated with CMM susceptibility in CMM families that do not have known mutations and are too small for linkage analyses.

The Contractor shall:

1.      Label DNA samples and hybridize them to Nimblegen whole-genome arrays;

2.      Include appropriate quality control step for the validity of the assay;

3.      Scan arrays, extract and process data, perform segmentation analysis using Nimblegen’s softwares;

4.      Deliver raw and processed data (including visualization software);

5.      Provide technical guidance and trouble shooting to the NCI Project Officer on the work performed under this procurement.

Roche NimbleGen offers the highest resolution array CGH platform on the market for analysis of DNA copy number. Unique features of Roche NimbleGen arrays include ultra-high density and long oligonucleotide probes that provide superior performance and data quality. The tiling-path designs provide comprehensive coverage of both genic and intergenic regions and are not limited to loci represented by SNP arrays. These unique features allow ultra-high resolution detection of small deletions and amplifications as well as breakpoint mapping to gene-level resolution, even in complex regions such as segmental duplication loci. The enhanced sensitivity of long oligonucleotide probes enables better signal-to-noise ratios compared to short probes. Long probes also provide a greater specificity and tolerance for mismatches to detect copy number changes in polymorphic regions of the genome. The success and reproducibility of Roche NimbleGen arrays have been demonstrated through series of publications on major scientific journals such as Nature Genetics, American Journal of Human Genetics, Proc Natl Acad Sci USA, and etc. Our recent experience with Roche NimbleGen arrays using the same design and arrays in another familial cancer project was extremely positive. Both laboratory assays and data analyses were performed with high quality and with short turnaround time. Their technical support was very helpful. In short, Roche NimbleGen possesses the unique and superb array platform which specifically fits our study design. The company provides a full-service package including both array experiments and bioinformatics data processing, which will free us from purchasing equipment and software and validating assays. All the work will be done in a timely manner, which is critical for the success of our ongoing efforts to identify disease-related CNVs as a novel mechanism.

This is not a solicitation for competitive quotations.  However, if any interested party believes it can perform the requirement as detailed they may submit a statement of capabilities. All information furnished shall be in writing and must contain sufficient detail to allow the NCI to determine if it can meet the above unique specifications described herein.  An original and one copy of the capability statement must be received in the contracting office by 11:00 am EDT, on November 14, 2008.  All questions must be in writing and must be emailed to Karri Mares at [email protected] faxed to (301) 402-4513. A determination by the Government not to compete this proposed contract based upon responses to this notice is solely within the discretion of the Government.  Information received will be considered solely for the purpose of determining whether to conduct a competitive procurement.  In order to receive an award from the NCI contractors must be registered in the Online Representations and Certifications Applications (ORCA).  Please refer to http://orca.bpn.gov    In addition; contractors must be registered in the Central Contractor Registration (CCR) www.ccr.gov. No collect calls will be accepted. Please reference NCI-90010-KM on all correspondence.