# US 8,785,131 B2 · Prognostic test for early stage non small cell lung cancer (NSCLC) > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,785,131 B2 - Document ID: US8785131B2 - Status: Granted - Kind: B2 - Application number: 12/268,797 - Filed: 2008-11-11 - Published: 2010-05-13 - Granted: 2014-07-22 - Earliest claimed: 2008-11-11 - Assignees: Abbott Laboratories - Applicants: Larry E. Morrison; John Coon - Inventors: Larry E. Morrison; John Coon - Web page: https://patentgrep.com/patent/US8785131B2 ## CPC - C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575) - C12Q 1/6841: In situ hybridisation - C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism - C12Q 2600/156: Polymorphic or mutational markers - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES ## Abstract The invention provides methods for identifying early stage non-small cell lung cancer (NSCLC) patients who will have a favorable prognosis for the recurrence of lung cancer after surgical resection. The invention is based on the discovery that assessment of chromosomal copy number abnormalities at chromosome 10q23.3 and centromere 10 can be used for prognostic classification. The invention preferably uses fluorescence in situ hybridization with fluorescently labeled nucleic acid probes to hybridize to patient samples to quantify the chromosomal copy number of the these genetic loci. The chromosome copy number can also be determined using, for example, PCR or array CGH. Assessment of the copy number abnormality patterns with a classifier based on the relative loss of 10q23.3 signals compared to the centromere 10 signals produced statistically significant prognostic classification for NSCLC. The ratio of PTEN/CEP 10 signals, using a cutoff of 0.80, was capable of dividing patients into a group of 41 (≧0.80) in which 33 (80.5%) had the favorable prognosis, and a group of 18 (<0.80) in which 6 (33.3%) had the favorable prognosis (p=0.0008). Median times to recurrence in the former and latter groups were 83.0 and 13.0 months, respectively (p<0.0001). ## Claims ### Claim 1 A method of determining prognosis of lung cancer in a human patient, the method comprising: (a) obtaining a biological sample from a human patient classified as having early stage non-small cell lung cancer; (b) contacting the biological sample with a set of chromosomal probes comprising at least two probes selected from the group consisting of a chromosome 10q23.3 locus specific probe and a chromosome 10 enumeration probe under conditions sufficient to enable hybridization of probes in the set to chromosomes in the sample, if any; (c) identifying a hybridization pattern of the set of chromosomal probes to the biological sample; and (d) determining prognosis of lung cancer in the subject based upon the hybridization pattern identified in step (c), wherein the hybridization pattern is identification of a ratio of the number of probe signals for the chromosome locus 10q23.3 to the number of probe signals of chromosome 10, wherein a ratio of less than 0.80 indicates non favorable prognosis. ### Claim 2 (depends on 1) The method of claim 1, wherein the biological sample comprises a lung tissue biopsy or resection. ### Claim 3 (depends on 1) The method of claim 1, wherein each of the chromosomal probes is directly labeled with a fluorescent label that can be separately detected. ### Claim 4 (depends on 1) The method of claim 1, wherein the biological sample is from a patient classified as having Stage 1b non-small cell lung cancer. ### Claim 5 (depends on 1) The method of claim 1, wherein the biological sample is from a patient classified as having Stage 2 non-small cell lung cancer. ### Claim 6 (depends on 1) The method of claim 1, wherein the contacting step (b) is performed on an automated instrument. ### Claim 7 (depends on 1) The method of claim 1 wherein the cutoff for the ratio, which divides the patient population into two groups of differing prognosis, is from about 0.6 to about 1.0. ### Claim 8 (depends on 1) The method of claim 1 where the cutoff for the ratio, which divides the patient population into two groups of differing prognosis, is about 0.8. ### Claim 9 (depends on 1) The method of claim 1, wherein the biological sample comprises a cytology sample. ### Claim 10 (depends on 1) The method of claim 1, wherein the chromosome 10q23.3 locus specific probe includes sequences that flank each end of phosphatase and tensin homolog (PTEN). ### Claim 11 A method of determining prognosis of lung cancer in a human patient, the method comprising: (a) obtaining a biological sample from a human patient classified as having early stage non-small cell lung cancer; (b) measuring in the biological sample both chromosome copy number at chromosome locus 10q23.3 and chromosome copy number for chromosome 10; and (c) determining prognosis of lung cancer in the subject based upon ratio of chromosome copy number at chromosome locus 10q23.3 to chromosome copy number for chromosome 10, wherein the cutoff for the ratio, which divides a patient population into two groups of differing prognosis, is from about 0.6 to about 1.0. ### Claim 12 (depends on 11) The method of claim 11, wherein the chromosome copy number at chromosome locus 10q23.3 and for chromosome 10 is measured by in situ hybridization. ### Claim 13 (depends on 11) The method of claim 11, wherein the chromosome copy number at chromosome locus 10q23.3 and for chromosome 10 is measured by polymerase chain reaction. ### Claim 14 (depends on 11) The method of claim 11, wherein the chromosome copy number at chromosome locus 10q23.3 and for chromosome 10 is measured by array comparative genomic hybridization.