MUM-1 protein expressed by multiple myeloma-related gene

Abstract

This invention provides a method of determining a chromosomal breakpoint in a subject suffering from multiple myeloma which comprises steps of: (a) obtaining a DNA sample from the subject suffering from multiple myeloma; (b) determining whether there is J and C disjunction in the immunoglobulin heavy chain gene in the obtained DNA sample; (c) obtaining a genomic library having clones which contain genomic DNA fragments from the DNA sample which shows positive J and C disjunction; (d) selecting and isolating clones of the obtained library which show positive hybridization with a probe which is capable of specifically hybridizing with the C but not the J region of the immunoglobulin heavy chain gene; (e) preparing fluorescent probes from the genomic DNA fragments of the isolated clones from step (d); (f) hybridizing said fluorescent probes with metaphase chromosomes; and (g) determining the identity of the chromosomes which are capable of hybridizing to said fluorescent probes, wherein the identification of a chromosome other than chromosome 14 would indicate that the chromosomal breakpoint is between chromosome 14 and the identified chromosome, thereby determining a chromosomal breakpoint in a subject suffering from multiple myeloma. This invention also provides the identified gene altered by a chromosomal breakpoint and various uses thereof.

Description

[0001] The invention disclosed herein was made with Government support under NIH Grant No. CA 44025. Accordingly, the U.S. [0002] Government has certain rights in this invention.BACKGROUND OF THE INVENTION [0003] Throughout this application, various references are referred to within parentheses. Disclosures of these publications in their entireties are hereby incorporated by reference into this application to more fully describe the state of the art to which this invention pertains. Full bibliographic citation for these references may be found at the end of this application, preceding the claims. [0004] Multiple myeloma (MM) is an incurable B cell tumor affecting B cell end-stage differentiation. Clinically, the course of MM is similar to end-stage plasma cell leukemia (PCL), i.e., there is an uncontrollable proliferation of myeloma cells accompanied by numerous complications, including hyperviscosity syndromes, hypercalcemia, infections, multiple bone fractures, and organ failure. ...

AI Technical Summary

Benefits of technology

This patent describes a method for identifying a chromosomal breakpoint in a subject with multiple myeloma using a DNA sample from the subject. The method involves obtaining a genomic library containing genomic DNA fragments from the DNA sample, selecting clones that show positive hybridization with a probe that can specifically hybridize with the C region of the immunoglobulin heavy chain gene, isolating the clones that show positive hybridization with the C region, preparing fluorescent probes from the isolated clones, and hybridizing the probes with metaphase chromosomes. The invention also provides a gene designated MUM-1 and a nucleic acid probe that specifically hybridizes with the MUM-1 gene. Additionally, the invention provides an antisense oligonucleotide that can prevent overexpression of the MUM-1 gene and a purified MUM-1 protein.

Problems solved by technology

In contrast, little is known about molecular alterations of human MM / PCL, due to the difficulty in cytogenetic analysis.

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