Methods for detecting human papilloma virus-associated cancers
The present invention provides probes and methods of use thereof in the diagnosis and/or prognosis of certain types of cancers, particularly human papillomavirus (HPV)-associated cancers. The probes are designed for hybridization with genomic material in a manner indicative of one or more aberrations in the genetic material present in the test sample. The identified aberrations are biomarkers of HPV-associated cancer. The methods of the invention comprise contacting a sample to one or more probes, allowing any genetic material in the sample to hybridize to the genomic regions provided in the probes, analyzing the hybridizations, and analyzing the hybridizations to identify detected aberrations as biomarkers indicative of HPV-associated cancer progression.
1. A probe set for detecting biomarkers in a sample indicative of HPV-associated precancer and cancer, said probe set consisting of a probe that hybridizes to 3q26, a probe that hybridizes to 5p15, a probe that hybridizes to 20q13, and a probe that hybridizes to cen7, wherein:
(a) the probe that hybridizes to 3q26 comprises a probe preparation of seven different nick-translated clones corresponding to chromosome 3, clones 1-7 of Table 4;
(b) the probe that hybridizes to 5p15 comprises a probe preparation of five different nick-translated clones corresponding to chromosome 5, clones 1-5 of Table 4;
(c) the probe that hybridizes to 20q13 comprises a probe preparation of three different nick-translated clones corresponding to chromosome 20, clones 1-3 of Table 4; and
(d) the probe that hybridizes to cen7 comprises a probe preparation of a nick-translated clone corresponding to chromosome 7, clone 1 of Table 4.
2. The probe set of claim 1 , wherein the HPV-associated precancer or cancer occurs in at least one human tissue selected from the group consisting of the cervix, the anus, the vulva, the vagina, the penis, oropharynx, and pharynx.
3. The probe set of claim 1 , wherein said probe that hybridizes to 3q26 is capable of hybridizing to SEQ ID NO: 1 or complement thereof.
4. The probe set of claim 1 , wherein said probe that hybridizes to 5p15 is capable of hybridizing to SEQ ID NO: 2 or complement thereof.
5. The probe set of claim 1 , wherein said probe that hybridizes to 20q13 is capable of hybridizing to SEQ ID NO: 3 or complement thereof.
6. The probe set of claim 1 , wherein said probe that hybridizes to cen7 is capable of hybridizing to SEQ ID NO: 4 or complement thereof.
7. The probe set of claim 1 , wherein each of the probes comprises a label capable of emitting a signal.
8. The probe set of claim 7 , wherein the signal is detectable by a human observer.
9. The probe set of claim 7 , wherein the signal is detectable by an analytical instrument.
10. The probe set of claim 7 , wherein the label comprises a moiety selected from the group consisting of fluorescent moieties, radioactive moieties, chromogenic moieties, and enzymatic moieties.
11. The probe set of claim 1 , wherein each of the probes is labeled with a different color fluorochrome.