Comparative genetic analysis of a rare synchronous collision tumor composed of malignant pleural mesothelioma and primary pulmonary adenocarcinoma.
BACKGROUND
Although asbestos acts as a potent carcinogen in pleural mesothelial and pulmonary epithelial cells, it still remains unclear whether asbestos causes specific and characteristic gene alterations in these different kinds of target cells, because direct comparison in an identical patient is not feasible. We experienced a rare synchronous collision tumor composed of malignant pleural mesothelioma (MPM) and primary pulmonary adenocarcinoma (PAC) in a 77-year-old man with a history of long-term smoking and asbestos exposure, and compared the DNA copy number alteration (CNA) and somatic mutation in these two independent tumors.


METHODS
Formalin-fixed paraffin-embedded (FFPE) tissues of MPM and PAC lesions from the surgically resected specimen were used. Each of these MPM and PAC lesions exhibited a typical histology and immunophenotype. CNA analysis using SNP array was performed using the Illumina Human Omni Express-12_FFPE (Illumina, San Diego, CA, USA) with DNA extracts from each lesion. Somatic mutation analysis using next-generation sequencing was performed using the TruSeq Amplicon Cancer Panel (Illumina).


RESULTS
The CNA analysis demonstrated a marked difference in the frequency of gain and loss between MPM and PAC. In PAC, copy number (CN) gain was detected more frequently and widely than CN loss, whereas in MPM there was no such obvious difference. PAC did not harbor CNAs that have been identified in asbestos-associated lung cancer, but did harbor some of the CNAs associated with smoking. MPM exhibited CN loss at 9p21.2-3, which is the most common genetic alteration in mesothelioma.


CONCLUSIONS
In this particular case, asbestos exposure may not have played a primary role in PAC carcinogenesis, but cigarette smoking may have contributed more to the occurrence of CN gains in PAC. This comparative genetic analysis of two different lesions with same amount of asbestos exposure and cigarette smoke exposure has provided information on differences in the cancer genome related to carcinogenesis.
Department of Surgical Pathology, Hokkaido University Hospital, Kita 14, Nishi 5, Kita-ku, Sapporo, Hokkaido, 060-8648, Japan.
Tomoaki
T
Naka
Department of Surgical Pathology, Hokkaido University Hospital, Kita 14, Nishi 5, Kita-ku, Sapporo, Hokkaido, 060-8648, Japan.|Research Division of Companion Diagnostics, Hokkaido University Hospital, Kita 14, Nishi 5, Kita-ku, Sapporo, Hokkaido, 060-8648, Japan.
Yutaka
Y
Hatanaka
Department of Surgical Pathology, Hokkaido University Hospital, Kita 14, Nishi 5, Kita-ku, Sapporo, Hokkaido, 060-8648, Japan.
Katsuji
K
Marukawa
Department of Surgical Pathology, Hokkaido University Hospital, Kita 14, Nishi 5, Kita-ku, Sapporo, Hokkaido, 060-8648, Japan.
Hiromi
H
Okada
Department of Surgical Pathology, Hokkaido University Hospital, Kita 14, Nishi 5, Kita-ku, Sapporo, Hokkaido, 060-8648, Japan.
Kanako C
KC
Hatanaka
First Department of Medicine, Hokkaido University School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
Jun
J
Sakakibara-Konishi
First Department of Medicine, Hokkaido University School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
Satoshi
S
Oizumi
Department of Cardiovascular and Thoracic Surgery, Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
Yasuhiro
Y
Hida
Department of Cardiovascular and Thoracic Surgery, Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
Kichizo
K
Kaga
Department of Surgical Pathology, Hokkaido University Hospital, Kita 14, Nishi 5, Kita-ku, Sapporo, Hokkaido, 060-8648, Japan.
Tomoko
T
Mitsuhashi
Department of Surgical Pathology, Hokkaido University Hospital, Kita 14, Nishi 5, Kita-ku, Sapporo, Hokkaido, 060-8648, Japan. ymatsuno@med.hokudai.ac.jp.|Research Division of Companion Diagnostics, Hokkaido University Hospital, Kita 14, Nishi 5, Kita-ku, Sapporo, Hokkaido, 060-8648, Japan. ymatsuno@med.hokudai.ac.jp.
Yoshihiro
Y
Matsuno
D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000077192:Adenocarcinoma of Lung; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D008654:Mesothelioma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000086002:Mesothelioma, Malignant; D009154:Mutation; D009378:Neoplasms, Multiple Primary / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests
D014408:Biomarkers, Tumor
Collision tumor; Copy number alteration; Malignant pleural mesothelioma