Detection of chromosomal abnormalities associated with prognosis of non small cell lung cancer

Abstract

The methods and compositions described herein address the need for a diagnostic method that can be provided to patients with early stage lung cancer, especially non-small cell lung cancer (NSCLC), to determine whether the patient is at increased risk of poor disease outcome. The methods and compositions thus allow for more informed treatment decisions for the early stage lung cancer patient.

1 .- 34 . (canceled) 
     
     
         35 . A method of predicting disease outcome in a patient being treated for lung cancer, from a biological sample from the patient, the method comprising:
 contacting the sample with two or more probes, each probe targeting a different chromosome subregion, wherein the chromosome subregion is selected from the group consisting of: 2q24.2, 2q33.3, 3q11.2, 3q13.32, 6q13, 6p21.2, 6q22.31, 8p23.1, 9p35.3, 11q13.1, 12p13.3, 17q25.1, 19q12, and 19q13.11;   incubating the two or more probes with the sample under conditions in which each probe binds selectively with a polynucleotide sequence on its target chromosome or chromosomal region to form a stable hybridization complex;   detecting hybridization of the two or more probes, wherein a hybridization pattern showing at least one gain or loss at a chromosomal region targeted by the probes is indicative of increased risk of poor disease outcome when compared to a baseline measure of disease outcome in patients having no gain or loss at the two or more chromosomal regions targeted by the two or more probes; and   administering an aggressive therapy to the patient that is indicated as having increased risk of poor disease outcome,   with the proviso that if the combination of probes comprises a probe for chromosome subregion 6p21.2, then the combination of probes does not include a probe for chromosome subregions 11q13.1 or 17q25.1.   
     
     
         36 . The method of  claim 35 , wherein the patient has a diagnosis of stage I-II non-small cell lung cancer (NSCLC). 
     
     
         37 . The method of  claim 35 , wherein the sample is contacted with a combination of at least three probes, each probe targeting a different chromosome subregion, wherein a hybridization pattern showing a gain or loss in one or more of the chromosome subregions is indicative of poor disease outcome in the patient. 
     
     
         38 . The method of  claim 35 , wherein the sample is contacted with a combination of at least four probes, each probe targeting a different chromosome subregion, wherein a hybridization pattern showing a gain or loss in one or more of these chromosome subregions is indicative of poor disease outcome in the patient. 
     
     
         39 . The method of  claim 35 , wherein the probe combination distinguishes samples comprising stage I-II NSCLC at increased risk of poor disease outcome from samples that do not comprise stage I-II NSCLC at increased risk of poor disease outcome with a sensitivity of at least 93% and a specificity of at least 90%, wherein the sensitivity and specificity is determined using p-values obtained by comparing a decrease in overall survival or in time to recurrence in a patient population with and without the probes. 
     
     
         40 . The method of  claim 39 , wherein the sensitivity is at least 95% and the specificity is at least 90.4%. 
     
     
         41 . The method of  claim 40 , wherein the sensitivity is at least 96% and the specificity is at least 91%. 
     
     
         42 . The method of  claim 35 , wherein the probe combination comprises ten probes or fewer. 
     
     
         43 . The method of  claim 35 , wherein the probe combination comprises eight probes or fewer. 
     
     
         44 . The method of  claim 35 , wherein the probe combination comprises four probes. 
     
     
         45 . The method of  claim 35 , wherein the method is carried out by array comparative genomic hybridization (aCGH) to probes immobilized on a substrate. 
     
     
         46 . The method of  claim 35 , wherein the method is carried out by fluorescence in situ hybridization (FISH), and each probe in the probe combination is labeled with a different fluorophore. 
     
     
         47 . The method of  claim 35 , wherein the sample comprises a lung biopsy specimen. 
     
     
         48 . The method of  claim 35 , wherein the aggressive therapy comprises adjuvant chemotherapy post-resection or neoadjuvant chemotherapy before resection. 
     
     
         49 . A combination of probes comprising 2, 3, 4, 5, 6, 7, 8, 9 or 10 probes selected from the group consisting of: 1p13.3, 2q24.2, 2q33.3, 3q11.2, 3q13.32, 6q13, 6p21.2, 6q22.31, 8p23.1, 9p35.3, 11q13.1, 12p13.3, 17q25.1, 19q12, and 19q13.11. 
     
     
         50 . The combination of probes of  claim 49 , wherein the combination of probes has a sensitivity of at least 93% and a specificity of at least 90% for distinguishing samples comprising stage I-II NSCLC at increased risk of poor disease outcome from samples that do not comprise stage I-II NSCLC at poor disease outcome. 
     
     
         51 . A kit for predicting disease outcome in a patient being treated for lung cancer, from a biological sample from the patient, wherein the kit comprises a combination of probes comprising between 2 and 10 probes selected from the group consisting of: 1p13.3, 2q24.2, 2q33.3, 3q11.2, 3q13.32, 6q13, 6p21.2, 6q22.31, 8p23.1, 9p35.3, 11q13.1, 12p13.3, 17q25.1, 19q12, and 19q13.11. 
     
     
         52 . The kit of  claim 51 , wherein the combination of probes has a sensitivity of at least 93% and a specificity of at least 90% for distinguishing samples comprising stage I-II NSCLC at increased risk of poor disease outcome from samples that do not comprise stage I-II NSCLC at poor disease outcome. 
     
     
         53 . The kit of  claim 52 , wherein the sensitivity is at least 95% and the specificity is at least 90.4%. 
     
     
         54 . The kit of  claim 53 , wherein the sensitivity is least 96% and the specificity is at least 91%.