Matthew Meyerson M.D., Ph.D.

Lay Description

Although most cases of lung cancer are associated with tobacco smoking, many lung cancers occur in non-smokers. The causes of lung carcinoma in non-smokers remain mysterious, but cancer-causing viruses are among possible causes. We plan to use a new method to identify disease-causing microbes, computational subtraction, to look for viruses that cause bronchioalveolar carcinoma. This sub-type of lung cancer occurs most frequently in people who have never smoked, compared to other lung cancer types. We will take bronchioalveolar cancer tissue and make libraries that represent the genes in the cancer tissue. We will then determine the sequence of DNA in those genes. This means that we will read the order of each nucleotide or "letter" in the DNA and find the exact DNA "words" that are written in the cancer tissue. We will then compare these sequences to the sequence of the human genome. DNA sequences from viruses are unlikely to match the human sequence. If we find such sequences, we can test whether possible viruses are specifically present in multiple cases of bronchioalveolar carcinoma.

Scientific Abstract

Although most cases of lung cancer are associated with tobacco smoking, many lung cancers occur in non-smokers. The causes of lung carcinoma in non-smokers remain mysterious, but cancer-causing viruses are among possible causes. We plan to use a new method to identify disease-causing microbes, computational subtraction, to look for viruses that cause bronchioalveolar carcinoma. This sub-type of lung cancer occurs most frequently in people who have never smoked, compared to other lung cancer types.

We propose the following experiments. 1) To generate cDNA and genomic DNA libraries from cases of bronchioalveolar carcinoma (BAC) from non-smoking patients (preferably women) in high-incidence areas. These libraries will be both conventional libraries as well as using a new concatenated method that we have developed. 2) To sequence these libraries to saturation and then to compare sequences computationally to the human genome. All sequences that match the human genome will be removed. The remaining sequences will be tested by PCR against both bronchioalveolar carcinoma and normal control specimens. 3) Those sequences that are BAC-specific by PCR will be tested for presence in multiple BAC specimens. Any sequences that are found in a high proportion of BAC specimens will be considered as candidate pathogen sequences.