*Article* **Identification of Clonality through Genomic Profile Analysis in Multiple Lung Cancers**

**Rumi Higuchi 1,**†**, Takahiro Nakagomi 1,2,**†**, Taichiro Goto 1,2,\*, Yosuke Hirotsu 3,**†**, Daichi Shikata 1, Yujiro Yokoyama 1,2, Sotaro Otake 1, Kenji Amemiya 3, Toshio Oyama 4, Hitoshi Mochizuki <sup>3</sup> and Masao Omata 3,5**


Received: 24 December 2019; Accepted: 16 February 2020; Published: 20 February 2020

**Abstract:** In cases of multiple lung cancers, individual tumors may represent either a primary lung cancer or both primary and metastatic lung cancers. In this study, we investigated the differences between clinical/histopathological and genomic diagnoses to determine whether they are primary or metastatic. 37 patients with multiple lung cancers were enrolled in this study. Tumor cells were selected from tissue samples using laser capture microdissection. DNA was extracted from those cells and subjected to targeted deep sequencing. In multicentric primary lung cancers, the driver mutation profile was mutually exclusive among the individual tumors, while it was consistent between metastasized tumors and the primary lesion. In 11 patients (29.7%), discrepancies were observed between genomic and clinical/histopathological diagnoses. For the lymph node metastatic lesions, the mutation profile was consistent with only one of the two primary lesions. In three of five cases with lymph node metastases, the lymph node metastatic route detected by genomic diagnosis differed from the clinical and/or pathological diagnoses. In conclusion, in patients with multiple primary lung cancers, cancer-specific mutations can serve as clonal markers, affording a more accurate understanding of the pathology of multiple lung cancers and their lymphatic metastases and thus improving both the treatment selection and outcome.

**Keywords:** lung cancer; multiple cancers; metastasis; sequencing; mutation; genomic diagnosis
