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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

Detection of ROS1-gene alterations in CTCs and tumor specimens from ROS1-rearranged patients. (A) Examples of ROS1-rearranged tumor cells in the tumor biopsy specimen and CTCs from patient P2. Green and red arrows show 3′ and 5′ ROS1-rearrangement extremities, respectively. Scale: white bars = 10 µm. (B) Tumor heterogeneity evaluated by enumerating ROS1-gene copies in tumor cells harboring a ROS1-rearrangement or only a gain of ROS1 native copies in baseline CTCs and tumor biopsies.
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MDV165F2: Detection of ROS1-gene alterations in CTCs and tumor specimens from ROS1-rearranged patients. (A) Examples of ROS1-rearranged tumor cells in the tumor biopsy specimen and CTCs from patient P2. Green and red arrows show 3′ and 5′ ROS1-rearrangement extremities, respectively. Scale: white bars = 10 µm. (B) Tumor heterogeneity evaluated by enumerating ROS1-gene copies in tumor cells harboring a ROS1-rearrangement or only a gain of ROS1 native copies in baseline CTCs and tumor biopsies.

Mentions: Next, patterns of ROS1 rearrangement were examined within paired biopsy specimens and CTCs of ROS1-rearranged patients (supplementary Table S1, available at Annals of Oncology online). As previously reported, two split patterns were detected in tumor biopsies consisting in either the split of green and red signals or isolated green signals [5, 6]. In contrast to tumor biopsies, both types of split pattern were identified in ROS1-rearranged CTCs, with gain of native ROS1 copies far more prevalent (Figure 2A, supplementary Table S1, available at Annals of Oncology online). This included an important subset of CTCs exclusively harboring a gain of native ROS1 copies (supplementary Table S1, available at Annals of Oncology online). In CTCs with both types of ROS1 split pattern, tumor heterogeneity, as assessed by ROS1 copy number, was significantly higher in CTCs compared with paired tumor biopsy in the three patients who experienced PR (P2, P4) or SD (P1) (P < 0.0001) (Figure 2B).Figure 2.


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)

Detection of ROS1-gene alterations in CTCs and tumor specimens from ROS1-rearranged patients. (A) Examples of ROS1-rearranged tumor cells in the tumor biopsy specimen and CTCs from patient P2. Green and red arrows show 3′ and 5′ ROS1-rearrangement extremities, respectively. Scale: white bars = 10 µm. (B) Tumor heterogeneity evaluated by enumerating ROS1-gene copies in tumor cells harboring a ROS1-rearrangement or only a gain of ROS1 native copies in baseline CTCs and tumor biopsies.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4478971&req=5

MDV165F2: Detection of ROS1-gene alterations in CTCs and tumor specimens from ROS1-rearranged patients. (A) Examples of ROS1-rearranged tumor cells in the tumor biopsy specimen and CTCs from patient P2. Green and red arrows show 3′ and 5′ ROS1-rearrangement extremities, respectively. Scale: white bars = 10 µm. (B) Tumor heterogeneity evaluated by enumerating ROS1-gene copies in tumor cells harboring a ROS1-rearrangement or only a gain of ROS1 native copies in baseline CTCs and tumor biopsies.
Mentions: Next, patterns of ROS1 rearrangement were examined within paired biopsy specimens and CTCs of ROS1-rearranged patients (supplementary Table S1, available at Annals of Oncology online). As previously reported, two split patterns were detected in tumor biopsies consisting in either the split of green and red signals or isolated green signals [5, 6]. In contrast to tumor biopsies, both types of split pattern were identified in ROS1-rearranged CTCs, with gain of native ROS1 copies far more prevalent (Figure 2A, supplementary Table S1, available at Annals of Oncology online). This included an important subset of CTCs exclusively harboring a gain of native ROS1 copies (supplementary Table S1, available at Annals of Oncology online). In CTCs with both types of ROS1 split pattern, tumor heterogeneity, as assessed by ROS1 copy number, was significantly higher in CTCs compared with paired tumor biopsy in the three patients who experienced PR (P2, P4) or SD (P1) (P < 0.0001) (Figure 2B).Figure 2.

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