演題番号 : O1-3
Lung cancer arises from the accumulation of genetic mutations, usually in exons. A recent study identified indel mutations in the noncoding region of surfactant-encoding genes in certain patients with lung adenocarcinoma (Cell, 2017, doi: 10.1016/j.cell.2016.12.025.). In addition, these noncoding indels were organ-specific and were identified in liver (albumin-encoding genes), gastric (lipase-encoding genes), and thyroid cancer (thyroglobulin-encoding genes).
The subjects were 86 patients with lung cancer (64 with adenocarcinoma, 14 with squamous cell carcinoma, and eight with other histological types) who underwent surgery in our department. The cancer panel was designed in our institution for analyzing noncoding regions. DNA was extracted from formalin-fixed, paraffin-embedded tumor tissue samples of surgical specimens, and targeted sequencing was performed.
Among the subjects, indels in the 3' untranslated region (3' UTR) of surfactant-encoding genes were identified in 18 (28.1%) of 64 patients with adenocarcinoma, three (21.4%) of 14 patients with squamous cell carcinoma, and one (12.5%) of eight patients with other histological types. Noncoding indels were not observed in albumin-, lipase-, and thyroglobulin-encoding genes. In patients with multiple cancers, the indels can be used as clonal markers to determine whether the tumor was a primary or metastasized lesion. In two patients with mediastinal lymph node cancer, lung cancer was determined as the primary site because of the presence of the indels.
Indels in the 3' UTR of surfactant-encoding genes represent the precise cell of origin for the lung cancer, irrespective of histological type and disease stage. In clinical practice, indels can be used as clonal markers in patients with multiple cancers and for determining the origin of cancer of unknown primary.