University of California

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Anne Kallioniemi

Joe W Gray

Daniel Pinkel

Olli-Pekka Kallioniemi

Frederic Waldman

Masaru Sakamoto

Ollie-Pekka Kallioniemi

Donna G Albertson

Ettore Appella

Albert J Fornace, Jr

Antoine M Snijders

Bing Huey

Jane Fridyland

Dmitry Bulavin

Ol'li-Pekka Kallioniemi

Frederick Waldman

Disclosed are new methods comprising the use of in situ hybridization to detect abnormal nucleic acid sequence copy numbers in one or more genomes wherein repetitive sequences that bind to multiple loci in a reference chromosome spread are either substantially removed and/or their hybridization signals suppressed. The invention termed Comparative Genomic Hybridization (CGH) provides for methods of determining the relative number of copies of nucleic acid sequences in one or more subject genomes or portions thereof (for example, a tumor cell) as a function of the location of those sequences in a reference genome (for example, a normal human genome). The intensity(ies) of the signals from each labeled subject nucleic acid and/or the differences in the ratios between different signals from the labeled subject nucleic acid sequences are compared to determine the relative copy numbers of the nucleic acid sequences in the one or more subject genomes as a function of position along the reference chromosome spread. Amplifications, duplications and/or deletions in the subject genome(s) can be detected. Also provided is a method of determining the absolute copy numbers of substantially all RNA or DNA sequences in subject cell(s) or cell population(s).

Detection of chromosomal abnormalities associated with breast cancer

Methods and compositions for staining based upon nucleic acid sequence that employnudeicnucleicacid probes are provided. Said methods produce staining patterns that can be tailored for specific cytogenetic analyses. Said probes are appropriate for in situ hybridization and stain both interphase and metaphase chromosomal material with reliable signals. The nucleic acid probes are typically of a complexity greater than 50 kb, the complexity depending upon the cytogenetic application. Methods and reagents are provided for the detection of genetic rearrangements. Probes and test kits are provided for use in detecting genetic rearrangements, particularly for use in tumor cytogenetics, in the detection of disease related loci, specifically cancer, such as chronic myelogenous leukemia (CML), retinoblastoma, ovarian and uterine cancers, and for biological dosimetry. Methods and reagents are described for cytogenetic research, for the differentiation of cytogenetically similar but genetically different diseases, and for many prognostic and diagnostic applications.

Chromosome-specific staining to detect genetic rearrangements associated with chromosome 3 and/or chromosome 17

Comparative genomic hybridization

The present invention provides a method of detecting nucleotide sequence differences between two nucleic acid samples. The method employs a comparative genomic hybridization (CGH) technique to analyze the sequence differences between the samples. This method permits the identification of small sequence differences (e.g., sequence divergence of 1% or less) in nucleic acid samples of high complexity (e.g., an entire genome).

Detection of nucleic acid sequence differences by comparative genomic hybridization

Isolated or purified oligonucleotides and isolated or purified morpholino oligomers; a method of detecting cancer or a predisposition to cancer in a mammal, comprising comparing the level of expression of Wip1 in the mammal to a control; a method of treating cancer in a mammal that expresses the same or a higher level of Wip1 as compared to a mammal of the same species that does not have cancer, comprising administering to the mammal a cancer-treating effective amount of a Wip1 inhibitor; a method of screening an oligonucleotide or morpholino oligomer for the ability to inhibit the expression of Wip1; a method of determining the efficacy with which a test oligonucleotide or morpholino oligomer inhibits Wip1 expression; a method of screening a compound for Wip1-inhibiting activity; and a method of determining the efficacy with which a test compound inhibits Wip1.

Materials and methods for inhibiting Wip1

Methods and compositions for staining based upon nucleic acid sequence that employ nucleic acid probes are provided. Said methods produce staining patterns that can be tailored for specific cytogenetic analyses. Said probes are appropriate for in situ hybridization and stain both interphase and metaphase chromosomal material with reliable signals. The nucleic acid probes are typically of a complexity greater than 50 kb, the complexity depending upon the cytogenetic application. Methods and reagents are provided for the detection of genetic rearrangements. Probes and test kits are provided for use in detecting genetic rearrangements, particularly for use in tumor cytogenetics, in the detection of disease related loci, specifically cancer, such as chronic myelogenous leukemia (CML), retinoblastoma, ovarian and uterine cancers, and for biological dosimetry. Methods and reagents are described for cytogenetic research, for the differentiation of cytogenetically similar but genetically different diseases, and for many prognostic and diagnostic applications.

Methods of staining target chromosomal DNA employing high complexity nucleic acid probes

Detection of chromosoal abnormalities associated with breast cancer

Methods and compositions for staining based upon nucleic acid sequence that employ nudeic acid probes are provided. Said methods produce staining patterns that can be tailored for specific cytogenetic analyses. Said probes are appropriate for in situ hybridization and stain both interphase and metaphase chromosomal material with reliable signals. The nucleic acid probes are typically of a complexity greater than 50 kb, the complexity depending upon the cytogenetic application. Methods and reagents are provided for the detection of genetic rearrangements. Probes and test kits are provided for use in detecting genetic rearrangements, particularly for use in tumor cytogenetics, in the detection of disease related loci, specifically cancer, such as chronic myelogenous leukemia (CML), retinoblastoma, ovarian and uterine cancers, and for biological dosimetry. Methods and reagents are described for cytogenetic research, for the differentiation of cytogenetically similar but genetically different diseases, and for many prognostic and diagnostic applications.

Comparative genomic hybridization (CGH)

Comparative Genomic Hybridization (CGH)

Growing community of inventors

Tampere, Finland

Anne Kallioniemi