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Comparative genetic analysis of a rare synchronous collision tumor composed of malignant pleural mesothelioma and primary pulmonary adenocarcinoma.

Naka T, Hatanaka Y, Marukawa K, Okada H, Hatanaka KC, Sakakibara-Konishi J, Oizumi S, Hida Y, Kaga K, Mitsuhashi T, Matsuno Y - Diagn Pathol (2016)

Bottom Line: 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.PAC did not harbor CNAs that have been identified in asbestos-associated lung cancer, but did harbor some of the CNAs associated with smoking.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgical Pathology, Hokkaido University Hospital, Kita 14, Nishi 5, Kita-ku, Sapporo, Hokkaido, 060-8648, Japan.

ABSTRACT

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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus

Karyotype of the synchronous collision tumor comparing MPM and PAC. Lines to the left of the chromosomes represent MPM and lines to the right represent PAC. Orange lines represent losses, green lines represent gains, and gray lines represent copy-neutral loss of heterozygosity (LOH). Loss of 9p21, which is the common genetic alterations in mesothelioma, was found in the MPM lesion (orange arrow)
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Fig3: Karyotype of the synchronous collision tumor comparing MPM and PAC. Lines to the left of the chromosomes represent MPM and lines to the right represent PAC. Orange lines represent losses, green lines represent gains, and gray lines represent copy-neutral loss of heterozygosity (LOH). Loss of 9p21, which is the common genetic alterations in mesothelioma, was found in the MPM lesion (orange arrow)

Mentions: In the MPM lesion, copy number (CN) gain was detected widely throughout almost the whole of chromosome 8 (Fig. 3). In addition, CN loss was detected in several limited regions in the long arm of chromosome 6 and at 9p21.2-3, both of which are the common genetic alterations in mesothelioma [2–6, 13]. Other short-region gains were found at 3q22-23, 9q34.2, 17q22-25, and 22q13.3, and losses were found at 1p31.2-1p12.1, 3p24.3, 4q21.13-22.1, 13q21.31, 13q33.3, and 15q22.2. Copy-neutral loss of heterozygosity (LOH) was found at 1p31.1, 2p16.2-16.1, 3p12.1, 5q14.3, 5p15.2, and 15q23-24.1. Gene alterations at 22q12.2 and 17p13.1 were not detected. Somatic mutation was observed in ATM (G2706A). Possible germline mutations of TP53 (P72R) and KDR (Q472H) were also observed in both MPM and PAC lesions with mutation rates of almost 50 % (data not shown).Fig. 3


Comparative genetic analysis of a rare synchronous collision tumor composed of malignant pleural mesothelioma and primary pulmonary adenocarcinoma.

Naka T, Hatanaka Y, Marukawa K, Okada H, Hatanaka KC, Sakakibara-Konishi J, Oizumi S, Hida Y, Kaga K, Mitsuhashi T, Matsuno Y - Diagn Pathol (2016)

Karyotype of the synchronous collision tumor comparing MPM and PAC. Lines to the left of the chromosomes represent MPM and lines to the right represent PAC. Orange lines represent losses, green lines represent gains, and gray lines represent copy-neutral loss of heterozygosity (LOH). Loss of 9p21, which is the common genetic alterations in mesothelioma, was found in the MPM lesion (orange arrow)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4836188&req=5

Fig3: Karyotype of the synchronous collision tumor comparing MPM and PAC. Lines to the left of the chromosomes represent MPM and lines to the right represent PAC. Orange lines represent losses, green lines represent gains, and gray lines represent copy-neutral loss of heterozygosity (LOH). Loss of 9p21, which is the common genetic alterations in mesothelioma, was found in the MPM lesion (orange arrow)
Mentions: In the MPM lesion, copy number (CN) gain was detected widely throughout almost the whole of chromosome 8 (Fig. 3). In addition, CN loss was detected in several limited regions in the long arm of chromosome 6 and at 9p21.2-3, both of which are the common genetic alterations in mesothelioma [2–6, 13]. Other short-region gains were found at 3q22-23, 9q34.2, 17q22-25, and 22q13.3, and losses were found at 1p31.2-1p12.1, 3p24.3, 4q21.13-22.1, 13q21.31, 13q33.3, and 15q22.2. Copy-neutral loss of heterozygosity (LOH) was found at 1p31.1, 2p16.2-16.1, 3p12.1, 5q14.3, 5p15.2, and 15q23-24.1. Gene alterations at 22q12.2 and 17p13.1 were not detected. Somatic mutation was observed in ATM (G2706A). Possible germline mutations of TP53 (P72R) and KDR (Q472H) were also observed in both MPM and PAC lesions with mutation rates of almost 50 % (data not shown).Fig. 3

Bottom Line: 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.PAC did not harbor CNAs that have been identified in asbestos-associated lung cancer, but did harbor some of the CNAs associated with smoking.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgical Pathology, Hokkaido University Hospital, Kita 14, Nishi 5, Kita-ku, Sapporo, Hokkaido, 060-8648, Japan.

ABSTRACT

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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus