Cellular arrays and methods of detecting and using genetic disorder markers

• US 20050244880A1
• Filed: 06/13/2005
• Published: 11/03/2005
• Est. Priority Date: 10/28/1998
• Status: Abandoned Application

• Current Assignee: United States Department Of Health And Human Services (Government of the United States of America)
• Original Assignee: United States Department Of Health And Human Services (Government of the United States of America)
• Inventors: Muller, Uwe Richard, Sauter, Guido, Kallioniemi, Olli-P, Barlund, Maarit, Kononen, Juha
• Application Number:
  US11/151,679
• Publication Number:
  US 20050244880A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/00743 Cells
• CPC Class Codes: B01L 3/5085 for multiple samples, e.g. microtitration plates
• CPC Class Codes: C12Q 1/6809 Methods for determination or identification of nucleic acids involving differential detection
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 1/6841 In situ hybridisation
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2537/157 A reaction step characterised by the number of molecules incorporated or released
• CPC Class Codes: C12Q 2539/103 Serial analysis of gene expression [SAGE]
• CPC Class Codes: C12Q 2543/10 the purpose being "in situ" analysis
• CPC Class Codes: C12Q 2565/501 being an array of oligonucleotides
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/112 Disease subtyping, staging or classification
• CPC Class Codes: C12Q 2600/118 Prognosis of disease development
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: G01N 1/08 involving an extracting tool, e.g. core bit
• CPC Class Codes: G01N 1/2813 Producing thin layers of samples on a substrate, e.g. smearing, spinning-on G01N1/30 takes precedence
• CPC Class Codes: G01N 1/312 for samples mounted on planar substrates
• CPC Class Codes: G01N 2001/282 with mapping; Identification of areas; Spatial correlated pattern
• CPC Class Codes: G01N 2001/288 : Filter punches
• CPC Class Codes: G01N 2001/368 : Mounting multiple samples in one block, e.g. TMA [Tissue Microarrays]
• CPC Class Codes: G01N 33/5005 : involving human or animal cells immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025
• CPC Class Codes: G01N 33/54306 : Solid-phase reaction mechanisms
• CPC Class Codes: G02B 21/34 : Microscope slides, e.g. mounting specimens on microscope slides

Abstract

A method is disclosed for rapid molecular profiling of tissue or other cellular specimens by placing a donor specimen in an assigned location in a recipient array, providing copies of the array, and performing a different biological analysis of each copy. The results of the different biological analyses are compared to determine if there are correlations between the results of the different biological analyses at each assigned location. In some embodiments, the specimens may be tissue specimens from different tumors, which are subjected to multiple parallel molecular (including genetic and immunological) analyses. The results of the parallel analyses are then used to detect common molecular characteristics of the genetic disorder type, which can subsequently be used in the diagnosis or treatment of the disease. The biological characteristics of the tissue can be correlated with clinical or other information, to detect characteristics associated with the tissue, such as susceptibility or resistance to particular types of drug treatment. Other examples of suitable tissues which can be placed in the matrix include tissue from transgenic or model organisms, or cellular suspensions (such as cytological preparations or specimens of liquid malignancies or cell lines).

Claims

1. A method of parallel analysis of tissue specimens, the method comprising:

obtaining a plurality of donor specimens;

placing each donor specimen in an assigned location in a recipient array;

using a genosensor comparative genomic hybridization (gCGH) array to identify a biomarker to test on the recipient array;

obtaining a plurality of sections from the recipient array in a manner that each section contains a plurality of donor specimens that maintain their assigned locations;

performing on each section a different biological analysis using the biomarker; and

comparing the results of the different biological analyses in corresponding assigned locations of different sections to determine if there are correlations between the results of the different biological analyses at each assigned location.

2. The method of claim 1, wherein the biomarker is selected by high-throughput genetic analysis.

3. The method of claim 1, wherein the biomarker comprises a numerical alteration of a chromosome, chromosomal region, gene, gene fragment, or locus.

4. The method of claim 1, wherein comparing the results comprises determining if there is an alteration of a gene by examining a marker for gene alteration.

5. The method of claim 4, wherein the alteration is an amplification of PDGFB in breast, lung, colon, testicular, endometrial, or bladder cancer.

6. A method of analyzing gene amplification in a tissue specimen, the method comprising:

screening multiple genes in a tissue specimen with a genosensor comparative genomic hybridization (gCGH) array that detects which genes are amplified in the tissue specimen; and

screening multiple tissue specimens in a tissue array with a nucleic acid probe to detect which genes are amplified in the tissue specimens;

wherein the result of screening multiple genes is used to select the nucleic acid probe to screen the multiple tissue specimens, or wherein the result of screening multiple tissue specimens is used to select the array that detects which genes are amplified.

7. The method of claim 6, wherein the gCGH array is assayed for a gene amplification, or a genetic or molecular marker that reflects this amplification.

8. The method of claim 7, wherein the gCGH array is a microarray that contains target loci that undergo amplification in cancer.

9. A method of analyzing a biological sample for a genetic disorder, the method comprising:

exposing a genosensor comparative genomic hybridization (gCGH) array of genomic regions to a nucleic acid sample from a cell with a known specific genetic disorder, and identifying as a biomarker a genomic region to which the nucleic acid hybridizes;

obtaining a candidate probe that hybridizes to the biomarker;

exposing the candidate probe to a tissue specimen array to determine a statistical measure of hybridization of the candidate probe;

selecting a candidate probe having a statistically significant measure of hybridization; and

using a selected candidate probe to analyze a biological sample for the genetic disorder.

10. The method of claim 9, wherein analysis of the biological sample provides diagnostic information.

11. The method of claim 9, wherein analysis of the biological sample provides prognostic information.

14. A method for detecting a genomic target sequence that is associated with a specific genetic disorder, the method comprising

contacting a plurality of genomic regions in a genosensor comparative genomic hybridization (gCGH) array with a nucleic acid test sample comprising nucleic acid fragments that collectively represent DNA from a cell with a known specific genetic disorder under conditions that allow the nucleic acid fragments to hybridize to one or more candidate genomic regions;

measuring the amount of nucleic acid test sample hybridized to the candidate genomic regions, if any, and selecting a candidate genomic region corresponding to an altered amount of hybridized test sample nucleic acid compared to a control sample of normal DNA;

preparing a nucleic acid probe that hybridizes to the selected candidate genomic region;

contacting a plurality of tissue samples with the probe under conditions that allow the probe to hybridize to nucleotide sequences in the tissue samples; and

selecting a candidate genomic region corresponding to a probe that hybridizes to a significant number of tissue samples as a genomic target sequence that is associated with the specific genetic disorder.