Compositions and methods for the diagnosis and prognosis of mesothelioma
The present invention provides nucleic acid sequences that are used for identification and diagnosis of specific cancers. The nucleic acid sequences can also be used for prognosis evaluation of a subject based on the expression profile of a biological sample.
1. A method to distinguish between pleural mesothelioma and adenocarcinoma in a human subject in need of treatment for lung cancer, and determine a therapeutic strategy based on the distinction between pleural mesothelioma and adenocarcinoma, the method comprising:
(a) obtaining lung samples from the human subject;
(b) extracting total RNA from the lung samples;
(c) determining the expression profile of SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 10 and SEQ ID NO: 11 in the lung samples by nucleic acid amplification using primer pairs comprising SEQ ID NOS: 29-32, 37 and 38, or sequences that are 90% identical to SEQ ID NOS: 29-32, 37 and 38, or by hybridization using a probe which is complimentary to SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 10 and SEQ ID NO: 11;
(d) normalizing said expression profile;
(e) distinguishing between pleural mesothelioma and adenocarcinoma based on the expression profile of SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 10 and SEQ ID NO: 11 in the lung samples relative to a reference threshold value, wherein an increase in the combined expression values of SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 10, and SEQ ID NO: 11 in the lung samples relative to a reference threshold value indicates that the human subject has pleural mesothelioma; and
(f) if determining a therapeutic strategy for said human subject in need of treatment for lung cancer based on the distinction between pleural mesothelioma and adenocarcinoma.
2. The method of claim 1 , wherein said adenocarcinoma originates from the lung.
3. The method of claim 2 , wherein said lung cancer is selected from the group consisting of lung squamous cell carcinoma, lung undifferentiated small cell carcinoma, lung undifferentiated large cell carcinoma, lung adenocarcinoma, nonsmall-cell lung cancer (NSCLC), lung carcinoid and neuroendocrine-large cell carcinoma.
4. The method of claim 1 , wherein said lung sample is a fluid or a tissue sample.
5. The method of claim 1 , wherein said lung sample is obtained from a human subject with cancer of unknown primary (CUP), with a primary cancer or with a metastatic cancer.
6. The method of claim 1 , wherein the step of distinguishing between pleural mesothelioma and adenocarcinoma is performed using a classifier algorithm.
7. A kit for distinguishing between pleural mesothelioma and adenocarcinoma, said kit comprising a set of probes comprising the reverse complementary sequence of SEQ ID NO: 2, SEQ ID NO: 3 and SEQ ID NO: 11 or a sequence that is 90% identical to said sequences.