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High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer.

Pailler E, Auger N, Lindsay CR, Vielh P, Islas-Morris-Hernandez A, Borget I, Ngo-Camus M, Planchard D, Soria JC, Besse B, Farace F - Ann. Oncol. (2015)

Bottom Line: Copy number in ROS1-rearranged CTCs increased significantly in two patients who progressed during crizotinib treatment (P < 0.02).CTCs from ROS1-rearranged patients had a high DNA content and gain of chromosomes, indicating high levels of aneuploidy and numerical CIN.We provide the first proof-of-concept that CTCs can be used for noninvasive and sensitive detection of ROS1 rearrangement in NSCLC patients.

View Article: PubMed Central - PubMed

Affiliation: INSERM U981 "Identification of Molecular Predictors and new Targets for Cancer Treatment", University of Paris-Sud XI, Gustave Roussy, Villejuif Translational Research Laboratory, Gustave Roussy, Villejuif.

No MeSH data available.


Related in: MedlinePlus

CIN status assessment in baseline CTCs from ROS1-rearranged patients. (A) Examples of CTCs with distinct epithelial and mesenchymal marker expression and high DNA content in a representative ROS1-rearranged patient. (B) Examples of hybridized WBCs and CTCs using fluorescently labeled probes. Green spots indicate probe hybridization at chromosome LSI 13 and CEP X, red spots at LSI 21 and CEP Y and blue spots at CEP 18. Scale: white bars = 10 µm. (C) Distribution of baseline CTC ploidy.
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MDV165F4: CIN status assessment in baseline CTCs from ROS1-rearranged patients. (A) Examples of CTCs with distinct epithelial and mesenchymal marker expression and high DNA content in a representative ROS1-rearranged patient. (B) Examples of hybridized WBCs and CTCs using fluorescently labeled probes. Green spots indicate probe hybridization at chromosome LSI 13 and CEP X, red spots at LSI 21 and CEP Y and blue spots at CEP 18. Scale: white bars = 10 µm. (C) Distribution of baseline CTC ploidy.

Mentions: As ROS1 FISH patterns within CTCs were strongly suggestive of the presence of highly aneuploid cells, we sought to characterize CTCs from ROS1-rearranged patients by means of two tests (DNA quantification by Hoechst 33342 measurement, multi-FISH assay) used to assess aneuploidy and numerical CIN status. CTCs from ROS1-rearranged patients were identified on filters as previously reported [18], and their DNA content determined relative to WBCs (Figure 4A, supplementary Table S2 and Figure S2, available at Annals of Oncology online). Immunofluorescence of CTCs revealed distinct epithelial and mesenchymal marker expression patterns, as well as high DNA content (Figure 4A). Numerical CIN status in CTCs from ROS1-rearranged patients was further characterized using the AneuVysion multi-FISH assay, which is used in prenatal diagnosis to enumerate chromosomes 13, 18, 21, X, and Y. Examples of chromosome 13, 18, 21, X and Y enumerations in CTCs are shown (Figure 4B). Patients P1, P2, and P4 had similar CTC profiles characterized by various stages of ploidy and the presence of highly aneuploid cells, while patient P3 had less CTCs bearing high ploidy (Figure 4C). Mean ploidy of CTCs in patients P1, P2, and P4 was approximately seven, while it was of 4.5 in patient P3 (supplementary Table S3, available at Annals of Oncology online). The four patients had the maximal numerical CIN score of 3.Figure 4.


High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer.

Pailler E, Auger N, Lindsay CR, Vielh P, Islas-Morris-Hernandez A, Borget I, Ngo-Camus M, Planchard D, Soria JC, Besse B, Farace F - Ann. Oncol. (2015)

CIN status assessment in baseline CTCs from ROS1-rearranged patients. (A) Examples of CTCs with distinct epithelial and mesenchymal marker expression and high DNA content in a representative ROS1-rearranged patient. (B) Examples of hybridized WBCs and CTCs using fluorescently labeled probes. Green spots indicate probe hybridization at chromosome LSI 13 and CEP X, red spots at LSI 21 and CEP Y and blue spots at CEP 18. Scale: white bars = 10 µm. (C) Distribution of baseline CTC ploidy.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4478971&req=5

MDV165F4: CIN status assessment in baseline CTCs from ROS1-rearranged patients. (A) Examples of CTCs with distinct epithelial and mesenchymal marker expression and high DNA content in a representative ROS1-rearranged patient. (B) Examples of hybridized WBCs and CTCs using fluorescently labeled probes. Green spots indicate probe hybridization at chromosome LSI 13 and CEP X, red spots at LSI 21 and CEP Y and blue spots at CEP 18. Scale: white bars = 10 µm. (C) Distribution of baseline CTC ploidy.
Mentions: As ROS1 FISH patterns within CTCs were strongly suggestive of the presence of highly aneuploid cells, we sought to characterize CTCs from ROS1-rearranged patients by means of two tests (DNA quantification by Hoechst 33342 measurement, multi-FISH assay) used to assess aneuploidy and numerical CIN status. CTCs from ROS1-rearranged patients were identified on filters as previously reported [18], and their DNA content determined relative to WBCs (Figure 4A, supplementary Table S2 and Figure S2, available at Annals of Oncology online). Immunofluorescence of CTCs revealed distinct epithelial and mesenchymal marker expression patterns, as well as high DNA content (Figure 4A). Numerical CIN status in CTCs from ROS1-rearranged patients was further characterized using the AneuVysion multi-FISH assay, which is used in prenatal diagnosis to enumerate chromosomes 13, 18, 21, X, and Y. Examples of chromosome 13, 18, 21, X and Y enumerations in CTCs are shown (Figure 4B). Patients P1, P2, and P4 had similar CTC profiles characterized by various stages of ploidy and the presence of highly aneuploid cells, while patient P3 had less CTCs bearing high ploidy (Figure 4C). Mean ploidy of CTCs in patients P1, P2, and P4 was approximately seven, while it was of 4.5 in patient P3 (supplementary Table S3, available at Annals of Oncology online). The four patients had the maximal numerical CIN score of 3.Figure 4.

Bottom Line: Copy number in ROS1-rearranged CTCs increased significantly in two patients who progressed during crizotinib treatment (P < 0.02).CTCs from ROS1-rearranged patients had a high DNA content and gain of chromosomes, indicating high levels of aneuploidy and numerical CIN.We provide the first proof-of-concept that CTCs can be used for noninvasive and sensitive detection of ROS1 rearrangement in NSCLC patients.

View Article: PubMed Central - PubMed

Affiliation: INSERM U981 "Identification of Molecular Predictors and new Targets for Cancer Treatment", University of Paris-Sud XI, Gustave Roussy, Villejuif Translational Research Laboratory, Gustave Roussy, Villejuif.

No MeSH data available.


Related in: MedlinePlus