Clonal and Parallel Evolution of Primary Lung Cancers and Their Metastases Revealed by Molecular Dissection of Cancer Cells

Takahashi, Kenji; Matsumoto, Shingo; Nakanishi, Yukihiro; Arai, Yasuhito; Yamamoto, Seiichiro; Fujiwara, Toshiyoshi; Tanaka, Noriaki; Yokota, Jun

doi:10.1158/1078-0432.ccr-06-0659

Cited by 31 publications

(42 citation statements)

References 39 publications

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“…Within individual patients, most mutations in primary tumors and metastases are identical, but some are unique to each; increasing degree of tumor cell chromosomal aberration correlates with more malignant properties; and recurrences contain the mutations seen before in primary tumors along with additional ones. 53,[59][60] Studies of pre-malignant lesions such as colorectal adenomas have similarly found that more mutations tend to occur in more advanced neoplasms, 61 indicating that clonal evolution likely occurs during tumorigenesis and may therefore continue during tumor progression.…”

Section: The Cancer Stem Cell Hypothesismentioning

confidence: 99%

Breast Tumor Heterogeneity: Cancer Stem Cells or Clonal Evolution?

Campbell

Polyák²

2007

Cell Cycle

365

272

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Breast tumors are composed of a variety of cell types with distinct morphologies and behaviors. It is not clear how this tumor heterogeneity comes about. Two popular concepts that attempt to explain this are the cancer stem cell hypothesis and the clonal evolution model. Each of these ideas has been investigated for some time, leading to the accumulation of numerous findings that are used to support one or the other. Although the two views share some similarities, they are fundamentally different notions with very different clinical implications. Analysis of the research backing each concept, along with a review of the results of our recent study investigating putative breast cancer stem cells, suggests how the cancer stem cell hypothesis and the clonal evolution model may be involved in generating breast tumor heterogeneity. An understanding of this process will allow the development of more effective ways to treat and prevent breast cancer.

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Section: The Cancer Stem Cell Hypothesismentioning

confidence: 99%

Breast Tumor Heterogeneity: Cancer Stem Cells or Clonal Evolution?

Campbell

Polyák²

2007

Cell Cycle

365

272

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“…5,6 Despite the widely accepted paradigm that tumor progression to metastasis occurs through linear clonal evolution, other mechanisms for this process have also been proposed. The parallel evolution model suggests that cells with metastatic potential separate from the primary tumor at an early stage in development and evolve independently from the primary tumor.7 Evidence supporting this has come from genomic analysis of breast and renal cell metastases, in which genetic profiles were found to be dissimilar to those of the primary tumors from the same patient.7-9 The parallel evolution model has also been used to explain the pattern of metastases in several other epithelial tumors, 3 although not ovarian cancer. However, in vivo studies argue against the viability of disseminated tumor cells; in a murine model, cells shed from tumors have reduced clonegenicity, resistance to apoptosis and to the formation of tumors.…”

mentioning

confidence: 99%

“…7-9 The parallel evolution model has also been used to explain the pattern of metastases in several other epithelial tumors, 3 although not ovarian cancer. However, in vivo studies argue against the viability of disseminated tumor cells; in a murine model, cells shed from tumors have reduced clonegenicity, resistance to apoptosis and to the formation of tumors.…”

mentioning

confidence: 99%

“…[1][2][3] The final step in this process is progression to metastasis, when 1 or more clonal populations of cancer cells have acquired sufficient genetic and functional changes to enable secondary tumor formation.…”

mentioning

confidence: 99%

“…7 Evidence supporting this has come from genomic analysis of breast and renal cell metastases, in which genetic profiles were found to be dissimilar to those of the primary tumors from the same patient. [7][8][9] The parallel evolution model has also been used to explain the pattern of metastases in several other epithelial tumors, 3 although not ovarian cancer. However, in vivo studies argue against the viability of disseminated tumor cells; in a murine model, cells shed from tumors have reduced clonegenicity, resistance to apoptosis and to the formation of tumors.…”

mentioning

confidence: 99%

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The clonal evolution of metastases from primary serous epithelial ovarian cancers

Khalique

Ayhan

Whittaker

et al. 2009

Intl Journal of Cancer

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Several models of evolution from primary cancers to metastases have been proposed; but the most widely accepted is the clonal evolution model proposed for colorectal cancer in which tumors develop by a process of linear clonal evolution driven by the accumulation of somatic genetic alterations. Various other models of cancer progression and metastasis have been proposed, including parallel evolution and the same gene model. The aim of this study was to investigate the evolution of metastases from primary cancer in 22 patients diagnosed with high-grade serous epithelial ovarian cancer. We established somatic genetic profiles based on the pattern of loss of heterozygosity, in several different regions of tumor tissue within the primary tumor and metastatic deposits from each case. Maximum parsimony tree analysis was used to examine the evolutionary relationship between the primary and metastatic samples for each patient. In addition, we investigated the extent of genetic heterogeneity within and between metastatic tumors compared with primary ovarian tumors. Our data suggest that most, if not all, metastases are clonally related to the primary tumors. However, the data oppose a single model of linear-clonal evolution whereby a late stage clone within the primary tumor acquires additional genetic changes that enable metastatic progression. Instead, the data support a model in which primary ovarian cancers have a common clonal origin, but become polyclonal, with different clones at both early and late stages of genetic divergence acquiring the ability to progress to metastasis. ' 2008 Wiley-Liss, Inc.Key words: ovarian cancer; genetic analysis; metastasis; clonal evolution; maximum parsimony; high-grade serous histology Genetic studies of colorectal cancer led Fearon and Vogelstein to propose that tumors develop by a process of clonal expansion driven by the accumulation of somatic genetic alterations, and this has become the most widely accepted model of tumor development.1-3 The final step in this process is progression to metastasis, when 1 or more clonal populations of cancer cells have acquired sufficient genetic and functional changes to enable secondary tumor formation.Epithelial cancers represent 90% of all malignant ovarian tumors; but the underlying genetic basis of ovarian tumor development remains poorly understood. This is partly because epithelial ovarian cancer is an extremely heterogeneous disease consisting of a wide spectrum of histological subtypes. There is mounting evidence that different molecular mechanisms are involved in the development of different ovarian tumor subtypes. Recent studies have also suggested that there is extensive genetic heterogeneity within ovarian tumors, which may hinder a better understanding of cancer development. Primary ovarian cancers tend to spread, at first, within the peritoneal cavity and the omentum, and are frequently associated with ascites, a fluid rich in growth factors and tumor cells disseminated from the primary cancer that fills the peritoneum. Tumor sp...

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KRAS mutation status in primary nonsmall cell lung cancer and matched metastases

Cortot

Italiano

Burel‐Vandenbos

et al. 2010

Cancer

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BACKGROUND:The objective of this study was to determine whether the mutation status of the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and epidermal growth factor receptor (EGFR) differed between primary tumors and matched distant metastases in nonsmall cell lung cancer (NSCLC). METHODS: Patients who underwent resection for both primary NSCLC and matched distant metastases were included in the study. KRAS and EGFR mutation status were assessed by polymerase chain reaction (PCR) amplification and direct sequencing on both primary tumors and metastases. For KRAS analysis, mutant-enriched PCR (ME-PCR) was performed in case of discordance between a primary tumor and its matched metastasis. RESULTS: Twenty-one patients were included. No EGFR mutations were detected. KRAS mutations were detected in 6 patients (28%). In all patients, the mutations identified by direct sequencing were discordant between the primary tumor and the matched metastasis. The use of ME-PCR allowed a resolution of the discordance in 3 of the 6 cases by demonstrating the presence of low levels of mutant KRAS in lesions that were negative by direct sequencing. CONCLUSIONS: Highly sensitive tools are required to identify biomarkers. The KRAS mutation status mostly was concordant between primary tumors and matched distant metastases. In a few patients, KRAS mutation status differed between different tumor sites. Cancer 2010;116:2682-7.

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Clonal and Parallel Evolution of Primary Lung Cancers and Their Metastases Revealed by Molecular Dissection of Cancer Cells

Cited by 31 publications

References 39 publications

Breast Tumor Heterogeneity: Cancer Stem Cells or Clonal Evolution?

Breast Tumor Heterogeneity: Cancer Stem Cells or Clonal Evolution?

The clonal evolution of metastases from primary serous epithelial ovarian cancers

KRAS mutation status in primary nonsmall cell lung cancer and matched metastases

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