MATERIALS AND METHODS FOR ASSESSING PROGRESSION OF PROSTATE CANCER

摘要

Methods of distinguishing and identifying a patient with aggressive/indolent, prostatic adenocarcinoma comprising contacting a sample from the patient with a set of detectably labeled probes under hybridization conditions and determining the presence of chromosomal abnormalities in the sample; sets of probes for use in such methods; and kits comprising a set of probes and instructions for distinguishing or identifying a patient as having aggressive/indolent, prostatic adenocarcinoma.

主权项

1. A method of distinguishing between a patient with aggressive, prostatic adenocarcinoma and a patient with indolent, prostatic adenocarcinoma, which method comprises:
(a) contacting a sample from the patient with:
(i) a set of detectably labeled probes consisting of a locus-specific probe for MYC and a locus-specific probe for FGFR1,(ii) a set of detectably labeled probes comprising a locus-specific probe for MYC, a locus-specific probe for FGFR1, and a break-apart probe for ERG,(iii) a set of detectably labeled probes comprising a locus-specific probe MYC, a locus-specific probe for FGFR1, a break-apart probe for ERG, and a locus-specific probe for PTEN,(iv) a set of detectably labeled probes comprising a locus-specific probe for MYC, a locus-specific probe for FGFR1, a break-apart probe for ERG, and a locus-specific probe for MYCN,(v) a set of detectably labeled probes comprising a locus-specific probe for MYC, a locus-specific probe for FGFR1, a break-apart probe for ERG, and a locus-specific probe for MDM2,(vi) a set of detectably labeled probes comprising a locus-specific probe for MYC, a locus-specific probe for FGFR1, a break-apart probe for ERG, and a locus-specific probe for NKX3.1,(vii) a set of detectably labeled probes comprising a locus-specific probe for MYC, a break-apart probe for ETV1, a locus-specific probe for FGFR1, and a locus-specific probe for P27,(viii) a set of detectably labeled probes comprising a locus-specific probe for MYC, a locus-specific probe for FGFR1, a locus-specific probe for PTEN, and a chromosome enumeration probe for chromosome 8 (CEP8),(ix) a set of detectably labeled probes comprising a chromosome enumeration probe for chromosome 8, a locus-specific probe for MYC, a break-part probe for ERG, and a locus-specific probe for FGFR1,(x) a set of detectably labeled probes comprising a chromosome enumeration probe for chromosome 8, a locus-specific probe for MYC, a break-apart probe for ERG, and a locus-specific probe for NKX3.1,(xi) a set of detectably labeled probes comprising a chromosome enumeration probe for chromosome 8, a locus-specific probe for MYC, a break-apart probe for ERG, and a locus-specific probe for FGFR1,(xii) a set of detectably labeled probes comprising a chromosome enumeration probe for chromosome 8, a locus-specific probe for MYC, a break-apart probe for ERG, and a locus-specific probe for MYCN,(xiii) a set of detectably labeled probes comprising a chromosome enumeration probe for chromosome 8, a locus-specific probe for MYC, a break-apart probe for ERG, and a locus-specific probe for MDM2,(xiv) a set of detectably labeled probes comprising a chromosome enumeration probe for chromosome 8, a locus-specific probe for MYC, a break-apart probe for ETV1, and a locus-specific probe for FGFR1,(xv) a set of detectably labeled probes comprising a locus-specific probe for AURKA, a locus-specific probe for MYC, a break-apart probe for ERG, and a locus-specific probe for FGFR1,(xvi) a set of detectably labeled probes comprising a chromosome enumeration probe for chromosome 8, a locus-specific probe for MYC, a break-apart probe for ERG, and a locus-specific probe for PTEN,(xvii) a set of detectably labeled probes comprising a locus-specific probe for MYC, a break-apart probe for ERG, a locus-specific probe for FGFR1, and a locus-specific probe for P27, or(xviii) a set of detectably labeled probes comprising a locus-specific probe for AURKA, a chromosome enumeration probe for chromosome 8, a locus-specific probe for MYC, and a break-apart probe for ERG,under hybridizing conditions,
wherein the locus-specific probe for FGFR1 in the sets of (i)-(vi), (viii), (xi), (xiv), (xv), and (xvii) is used to determine % loss of FGFR1, wherein the locus-specific probe for FGFR1 in the sets of (vii), (ix), and, as an alternative to % loss of FGFR1, (xiv), is used to determine % gain of FGFR1, wherein CEP8 in the sets of (ix)-(xiv), (xvi), and (xviii) is used to determine % loss of CEP8, wherein the locus-specific probe for PTEN in sets (iii) and (viii) is used to determine homozygous loss of PTEN, wherein the locus-specific probe for PTEN in set (xvi) is used to determine % loss of PTEN, and wherein the locus-specific probe for FGFR1 and CEP8 in the sets of (viii), and as an alternative to % gain of FGFR1, (ix), are used to determine % loss of FGFR1/CEP8 ratio, and (b) determining the presence of a chromosomal abnormality in the sample, wherein a MYC % gain (% gain is % of cells with MYC copy numbers >2) of greater than or equal to two to less than or equal to 30, wherein a FGFR1% loss (% loss is % of cells with FGFR copy numbers <2) of greater than or equal to 15 to less than or equal to 40, wherein a FGFR1% gain (% gain is % of cells with FGFR copy numbers >2) of greater than or equal to two to less than or equal to 46, wherein a CEP8% loss (% loss is % of cells with CEP8 copy numbers <2) of greater than or equal to 21 to less than or equal to 36, wherein a CEP8% gain (% gain is % of cells with CEP8 copy numbers >2) of greater than or equal to 15 to less than or equal to 40, wherein a FGFR1/CEP8% loss of greater than or equal to 13 to less than or equal to 72, wherein a PTEN % homozygous loss (% homozygous loss is % of cells with PTEN copy numbers of zero) of greater than or equal to two and less than or equal to 40, wherein a PTEN % loss (% loss is % of cells with PTEN copy number of less than two) of greater than or equal to 10 to less than or equal to 50, wherein a ERG 2+Edel of greater than or equal to one to less than or equal to 30, wherein a MYCN % gain (% gain is % of cells with MYCN copy numbers >2) of greater than or equal to two to less than or equal to 30, wherein a MDM2% gain (% gain is % of cells with MDM2 copy numbers >2) of greater than or equal to two to less than or equal to 20, wherein a NKX3.1% loss (% loss is % of cells with NKX3.1 copy numbers <2) of greater than or equal to 10 to less than or equal to 50, wherein an ETV1% translocation/deletion of greater than or equal to 1 to less than or equal to 20, wherein a P27% loss (% loss is % of cells with P27 copy numbers <2) of greater than or equal to 10 to less than or equal to 50, or wherein an AURKA % gain (% gain is % of cells with AURKA copy numbers >2) of greater than or equal to 1 to less than or equal to 20 indicates that the patient has a high risk of developing aggressive, prostatic adenocarcinoma, whereas none of the above indicates that the patient has indolent, prostatic adenocarcinoma, whereupon a patient with aggressive, prostatic adenocarcinoma is distinguished from a patient with indolent, prostatic adenocarcinoma.