Dataset Information

Cell migration leads to spatially distinct but clonally related airway cancer precursors.

ABSTRACT:

Background

Squamous cell carcinoma of the lung is a common cancer with 95% mortality at 5?years. These cancers arise from preinvasive lesions, which have a natural history of development progressing through increasing severity of dysplasia to carcinoma in situ (CIS), and in some cases, ending in transformation to invasive carcinoma. Synchronous preinvasive lesions identified at autopsy have been previously shown to be clonally related.

Methods

Using autofluorescence bronchoscopy that allows visual observation of preinvasive lesions within the upper airways, together with molecular profiling of biopsies using gene sequencing and loss-of-heterozygosity analysis from both preinvasive lesions and from intervening normal tissue, we have monitored individual lesions longitudinally and documented their visual, histological and molecular relationship.

Results

We demonstrate that rather than forming a contiguous field of abnormal tissue, clonal CIS lesions can develop at multiple anatomically discrete sites over time. Further, we demonstrate that patients with CIS in the trachea have invariably had previous lesions that have migrated proximally, and in one case, into the other lung over a period of 12?years.

Conclusions

Molecular information from these unique biopsies provides for the first time evidence that field cancerisation of the upper airways can occur through cell migration rather than via local contiguous cellular expansion as previously thought. Our findings urge a clinical strategy of ablating high-grade premalignant airway lesions with subsequent attentive surveillance for recurrence in the bronchial tree.

SUBMITTER: Pipinikas CP

PROVIDER: S-EPMC4033139 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Publications

Cell migration leads to spatially distinct but clonally related airway cancer precursors.

Pipinikas Christodoulos P CP Kiropoulos Theodoros S TS Teixeira Vitor H VH Brown James M JM Varanou Aikaterini A Falzon Mary M Capitanio Arrigo A Bottoms Steven E SE Carroll Bernadette B Navani Neal N McCaughan Frank F George Jeremy P JP Giangreco Adam A Wright Nicholas A NA McDonald Stuart A C SA Graham Trevor A TA Janes Sam M SM

Thorax 20140218 6

<h4>Background</h4>Squamous cell carcinoma of the lung is a common cancer with 95% mortality at 5 years. These cancers arise from preinvasive lesions, which have a natural history of development progressing through increasing severity of dysplasia to carcinoma in situ (CIS), and in some cases, ending in transformation to invasive carcinoma. Synchronous preinvasive lesions identified at autopsy have been previously shown to be clonally related.<h4>Methods</h4>Using autofluorescence bronchoscopy t ...[more]

PMID: 24550057

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Project description:ImportanceMerkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma. In rare cases, the development of an additional cutaneous MCC tumor is clinically consistent with a second primary MCC tumor rather than a cutaneous metastasis, which has important treatment and prognostic implications.ObjectiveTo evaluate genetic relatedness in 4 cases with the clinical diagnosis of multiple primary MCCs.Design, setting, and participantsIn this case series, 7 cases of clinically designated multiple primary MCC were identified; 4 cases met inclusion criteria for next-generation sequencing (NGS) analysis. Mutations, copy number alterations, and Merkel cell polyomavirus (MCPyV) sequence were analyzed and compared between clinically designated multiple primary tumors to characterize genetic relatedness and hence assess clonality. Patients with clinically designated multiple primary MCC were identified from the multidisciplinary MCC Program at the University of Michigan, a tertiary care center.Main outcomes and measuresFour cases of clinically designated multiple primary MCC were characterized by tumor sequencing and targeted MCPyV sequencing to distinguish independent primary tumors from related metastases.ResultsOverall, 4 patients in their 70s or 80s were included and analyzed. Cases 1 and 4 were verified as genetically distinct primary tumors and did not harbor similar copy number alterations or demonstrate significant mutational overlap. Cases 2 and 3 were designated as clonally related based on overlapping copy number alterations. In clonally related tumors, chromosomal copy number changes were more reliable than mutations for demonstrating clonality. Regardless of clonality, we found that MCPyV status was concordant for all tumor pairs and MCPyV positive tumors harbored predominatly subclonal mutations.Conclusions and relevanceOur findings suggest that patients with MCC may develop a second genetically distinct primary tumor; in this case, the subsequent tumor is likely to develop through similar mechanisms of pathogenesis, either MCPyV-mediated or ultraviolet light-mediated. Next-generation sequencing analysis of chromosomal copy number changes and mutations is useful in distinguishing multiple primary MCCs from progression of MCC clinically resembling multiple primaries, allowing appropriate staging of the patient.

Dataset Information

Cell migration leads to spatially distinct but clonally related airway cancer precursors.

Background

Methods

Results

Conclusions

Publications

Cell migration leads to spatially distinct but clonally related airway cancer precursors.

Similar Datasets

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