Omic Approach in Non-smoker Female with Lung Squamous Cell Carcinoma Pinpoints to Germline Susceptibility and Personalized Medicine / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Lung cancer is strongly associated to tobacco smoking. However, global statistics estimate that in females the proportion of lung cancer cases that is unrelated to tobacco smoking reaches fifty percent, making questionable the etiology of the disease. MATERIALS AND METHODS: A never-smoker female with primary EGFR/KRAS/ALK-negative squamous cell carcinoma of the lung and their normal sibswere subjected to a novel integrative “omic” approach using a pedigree-based model for discovering genetic factors leading to cancer in the absence of well-known environmental trigger. A first-stepwhole-exome sequencing on tumor and normal tissue did not identify mutations in known driver genes. Building on the idea of a germline oligogenic origin of lung cancer, we performed whole-exome sequencing of DNA from patients' peripheral blood and their unaffected sibs. Finally, RNA-sequencing analysis in tumoral and matched non-tumoral tissues was carried out in order to investigate the clonal profile and the pathogenic role of the identified variants. RESULTS: Filtering for rare variants with Combined Annotation Dependent Depletion (CADD) > 25 and potentially damaging effect, we identified rare/private germline deleterious variants in 11 cancer-associated genes, none ofwhich, except one, sharedwith the healthy sib, pinpointing to a “private” oligogenic germline signature. Noteworthy, among these, two mutated genes, namely ACACA and DEPTOR, turned to be potential targets for therapy because related to known drivers, such as BRCA1 and EGFR. CONCLUSION: In the era of precision medicine, this report emphasizes the importance of an “omic” approach to uncover oligogenic germline signature underlying cancer development and to identify suitable therapeutic targets as well.

Outcome in excised thymomas: role of prognostic factors and impact of additional malignancies on survival.

BACKGROUND AND AIMS: Although the management of thymomas has been extensively evaluated, the value of prognostic factors in the outcome of these patients remains unclear. METHODS AND RESULTS: The medical records of all patients who underwent resection of thymoma between January 1985 and September 2010 at a single thoracic unit were reviewed. Patients were followed up with reference to disease recurrence and development of additional malignancies (AM). Total thymectomy was performed in all 68 cases. Mean follow-up time was four years. Mean survival was 63.9 months. Mean disease-free interval was 13 months. Factors affecting prognosis were Masaoka staging and WHO histological sub-type. Patients with thymomas had a higher risk of developing AM when compared with a control population of individuals with other tumours (p = 0.0002). Among thymomas, the cortical subtype was associated with a higher risk of AM (p = 0.047) and mortality (p = 0.001). CONCLUSIONS: This data confirms that Masaoka staging and WHO histologic sub-type are the most important prognostic factors in patients with thymoma. Moreover, thymomas predominantly arising from the thymic cortex are associated with a higher risk of developing other malignancies and with poorer survival. The cortical origin of thymoma could therefore be considered as a significant prognostic factor.