Whole-exome sequencing to identify novel somatic mutations in squamous cell lung cancers.

Squamous cell lung cancer is a major histotype of non-small cell lung cancer (NSCLC) that is distinct from lung adenocarcinoma. We used whole-exome sequencing to identify novel non-synonymous somatic mutations in squamous cell lung cancer. We identified 101 single-nucleotide variants (SNVs) including 77 non-synonymous SNVs (67 missense and 10 nonsense mutations) and 11 INDELs causing frameshifts. We also found four SNVs located within splicing sites. We verified 62 of the SNVs (51 missense, 10 nonsense and 1 splicing-site mutation) and 10 of the INDELs as somatic mutations in lung cancer tissue. Sixteen of the mutated genes were also mutated in at least one patient with a different type of lung cancer in the Catalogue of Somatic Mutation in Cancer (COSMIC) database. Four genes (LPHN2, TP53, MYH2 and TGM2) were mutated in approximately 10% of the samples in the COSMIC database. We identified two missense mutations in C10orf137 and MS4A3 that also occurred in other solid-tumor tissues in the COSMIC database. We found another somatic mutation in EP300 that was mutated in 4.2% of the 2,020 solid-tumor samples in the COSMIC database. Taken together, our results implicate TP53, EP300, LPHN2, C10orf137, MYH2, TGM2 and MS4A3 as potential driver genes of squamous cell lung cancer.

[A clinical study of 49 cases of invasive pulmonary aspergillosis].

OBJECTIVE: Studying the proven and probable invasive pulmonary aspergillosis (IPA) cases of some hospitals in Shanghai to provide evidence for the improvement of IPA clinical diagnosis and therapy. METHODS: Forty-nine IPA cases were retrospectively analyzed for demography data, host factors, underlying conditions, chest CT, microorganism and histopathology examination, as well as therapy and clinical outcome. RESULTS: Of 49 subjects including 19 (38.8%) proven and 30 (61.2%) probable IPA, 3 patients (6.1%) had no host factors, 25 patients (51.0%) had IPA associated host factors and underlying conditions, while 21 patients (42.9%) had uncertain fundamental diseases. Chest CT evaluation demonstrated that radiological lesions include nodules in 29 patients, patching in 15, mass in 12, consolidation in 10, cavitation in 34, Halo sign in 19, air bronchogram in 18, crescentic sign in 6, bilateral in 33 and multifocal lesions in 38. The yielding rate of fungus culture in sputum was 26.5% (13/49), and in bronchoalveolar lavage fluid was 66.7% (10/15). Eleven of thirty-six patients (30.6%) had positive results of serum galactomannan antigen tests. Nineteen of twenty-one patients (90.5%) were proven as IPA by lung histologic examinations. Aspergillus fumigatus was the most common pathogen 81.0% (17/21). The responding rate to initial anti-fungus therapy was 50% (21/42). CONCLUSION: Our study suggests that in IPA patients, bilateral, multifocal and nodular lesion could be the most common radiological characteristic, while Halo and crescentic sign occur occasionally. Invasive technologies are more valuable to IPA diagnosis.