Compositions and methods for the treatment of prostate carcinoma
Compositions and methods for the diagnosis, treatment and prevention of prostate cancer, well as for treatment selection.
1. A method of and treating prostate cancer in a subject, the method comprising:
(a) detecting an alteration in a HoxB13 nucleic acid sequence or amino acid sequence in a biological sample obtained from the subject, wherein the alteration in HOXB13 is selected from the group consisting of:
a change of adenosine for guanine in the second position of codon 84 (GGA-GAA) resulting in a nonconservative substitution of glutamic acid for glycine (G84E);
a missense mutation 685C-G resulting in the substitution of glycine for arginine at position 229 (R229G);
a substitution mutation 431T-C resulting in a substitution of leucine for proline (L144P); and
a substitution of aspartic acid for tyrosine (Y88D) at codon 88 (262T-G), and
(b) administering a therapeutic regimen selected from the group consisting of radical prostatectomy, radiation therapy, hormone therapy and chemotherapy, for treating the subject.
2. The method of claim 1 , wherein the subject is further identified as having a positive family history for prostate cancer and is younger than age 55.
3. The method of claim 1 , wherein the G84E mutation alteration is identified in a subject of Nordic descent.
4. The method of claim 1 , wherein the R229G mutation is identified in a subject of African-American descent.
5. The method of claim 1 , wherein the sample is a tissue sample, tissue biopsy sample, or biological liquid.
6. The method of claim 1 , wherein said method identifies the subject as in need of increased surveillance for prostate disease.
7. The method of claim 5 , wherein said surveillance comprises annual measurement of PSA levels in said subject.
8. The method of claim 1 , further comprising administering a PSA test to the subject and detecting elevated PSA levels in the subject.
9. The method of claim 1 , wherein said detecting comprises annealing an amplification product to a fluorescent hybridization probe selected from the group consisting of a 5′ nuclease probe oligonucleotide containing a 5′ fluorescent dye and 3′ quenching dye, a molecular beacon and a FRET hybridization probe.
10. The method of claim 9 , wherein the 5′ nuclease probe oligonucleotide containing a 5′ fluorescent dye and 3 quenching dye comprises the GGA to GAA variant of SEQ ID NO: 4.