Chromosomal alterations in small cell lung cancer revealed by multicolour fluorescence <i>in situ</i> hybridization

Ashman, J. N. E.; Brigham, J.; Cowen, Michael E.; Bahia, H.; Greenman, John; Lind, Michael; Cawkwell, Lynn

doi:10.1002/ijc.10704

Cited by 29 publications

(12 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…G, interphase FISH using centromeres 3 (red), 7 (green), 17 FISH of the original tumor showed that its ploidy status was the same as that of the engraftments and confirmed CGH findings. Finally, the squamous cell carcinoma, LU16-SQCC, also showed a complex karyotype consistent with findings from other cytogenetic descriptions of SQCCs (23). FISH analysis of the original tumor specimen was consistent with the SKY findings in the xenograft, specifically, the detection of two copies of 9p21 in the original specimen corresponding to the clonal loss of 9p in one of the three chromosome 9 homologues.…”

Section: Lu13-cas Tumor Before Graftsupporting

confidence: 86%

Establishment in Severe Combined Immunodeficiency Mice of Subrenal Capsule Xenografts and Transplantable Tumor Lines from a Variety of Primary Human Lung Cancers: Potential Models for Studying Tumor Progression–Related Changes

Cutz

Guan²,

Bayani³

et al. 2006

Clinical Cancer Research

105

View full text Add to dashboard Cite

Purpose: Lung cancer is a biologically diverse disease and relevant models reflecting its diversity would facilitate the improvement of existing therapies. With a view to establishing such models, we developed and evaluated xenografts of a variety of human lung cancers. Experimental Design: Using nonobese diabetic/severe combined immunodeficiency mice, subrenal capsule xenografts were generated from primary lung cancer tissue, including moderately and poorly differentiated squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, small cell carcinoma, large cell undifferentiated carcinoma, and carcinosarcoma. After 4 to 12 weeks, xenografts were harvested for serial transplantation and comparison with the original tissue via histologic, chromosomal, and cytogenetic analyses. Results: Xenografts were successfully established. H&E staining showed that xenografts retained major histologic features of the original cancers. Immunohistochemistry and fluorescence in situ hybridization confirmed the human origin of the tumor cells and development in xenografts of murine supportive stroma. Four transplantable lines were developed from rapidly growing tumors (>5 generations), i.e., a small cell lung carcinoma, large cell undifferentiated carcinoma, pulmonary carcinosarcoma, and squamous cell carcinoma. Analyses including spectral karyotyping, comparative genomic hybridization, and fluorescence in situ hybridization, revealed that the xenografts were genetically similar to the original tumors, showing chromosomal abnormalities consistent with karyotypic changes reported for lung cancer. Conclusions: The subrenal capsule xenograft approach essentially provides a living tumor bank derived from patient material and a means for isolating and expanding specific cell populations. The transplantable tumor lines seem to provide good models for studying various aspects of tumor progression and a platform for developing novel therapeutic regimens, with the possibility of patient-tailored therapies.

show abstract

Section: Lu13-cas Tumor Before Graftsupporting

confidence: 86%

Establishment in Severe Combined Immunodeficiency Mice of Subrenal Capsule Xenografts and Transplantable Tumor Lines from a Variety of Primary Human Lung Cancers: Potential Models for Studying Tumor Progression–Related Changes

Cutz

Guan²,

Bayani³

et al. 2006

Clinical Cancer Research

105

View full text Add to dashboard Cite

show abstract

“…Mutations and amplifications in the epidermal growth factor receptor (EGFR) kinase domain were shown to correlate with the response to erlotinib and gefitinib (6,(11)(12)(13)(14). Unfortunately, no such progress has been achieved with SCLC, although genomic analysis of SCLC has been reported (15)(16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

Integrative Genomic Analysis of Small-Cell Lung Carcinoma Reveals Correlates of Sensitivity to Bcl-2 Antagonists and Uncovers Novel Chromosomal Gains

Olejniczak

Sant²,

Anderson³

et al. 2007

Molecular Cancer Research

View full text Add to dashboard Cite

Cancer is a highly heterogeneous disease in terms of the genetic profile and the response to therapeutics. An early identification of a genomic marker in drug discovery may help select patients that would respond to treatment in clinical trials. Here we suggest coupling compound screening with comparative genomic hybridization analysis of the model systems for early discovery of genomic biomarkers. A Bcl-2 antagonist, ABT-737, has recently been discovered and shown to induce regression of solid tumors, but its activity is limited to a fraction of small-cell lung carcinoma (SCLC) models tested. We used comparative genomic hybridization on high-density single-nucleotide polymorphism genotyping arrays to carry out a genome-wide analysis of 23 SCLC cell lines sensitive and resistant to ABT-737. The screen revealed a number of novel recurrent gene copy number abnormalities, which were also found in an independent data set of 19 SCLC tumors and confirmed by real-time quantitative PCR. A previously unknown amplification was identified on 18q and associated with the sensitivity of SCLC cell lines to ABT-737 and another Bcl-2 antagonist. The region of gain contains Bcl-2 and NOXA, two apoptosis-related genes. Expression microarray profiling showed that the genes residing in the amplified region of 18q are also overexpressed in the sensitive lines relative to the resistant lines. Fluorescence in situ hybridization analysis of tumors revealed that Bcl-2 gain is a frequent event in SCLC. Our findings suggest that 18q21-23 copy number will be a clinically relevant predictor for sensitivity of SCLC to Bcl-2 family inhibitors. The 18q21-23 genomic marker may have a broader application in cancer because Bcl-2 is associated with apoptosis evasion and chemoresistance.

show abstract

“…Multiple regions on this chromosome arm have been implicated in SCLC and non-small-cell lung cancer (NSCLC) (Girard et al, 2000;Nomoto et al, 2000;Chizhikov et al, 2001;Ashman et al, 2002). Here, we describe the construction of a unique resource for analysing 1p.…”

mentioning

confidence: 99%

Genomic and gene expression profiling of minute alterations of chromosome arm 1p in small-cell lung carcinoma cells

et al. 2005

View full text Add to dashboard Cite

Genetic alterations occurring on human chromosome arm 1p are common in many types of cancer including lung, breast, neuroblastoma, pheochromocytoma, and colorectal. The identification of tumour suppressors and oncogenes on this arm has been limited by the low resolution of current technologies for fine mapping. In order to identify genetic alterations on 1p in small-cell lung carcinoma, we developed a new resource for fine mapping segmental DNA copy number alterations. We have constructed an array of 642 ordered and fingerprint-verified bacterial artificial chromosome clones spanning the 120 megabase (Mb) 1p arm from 1p11.2 to p36.33. The 1p arm of 15 small-cell lung cancer cell lines was analysed at sub-Mb resolution using this arm-specific array. Among the genetic alterations identified, two regions of recurrent amplification emerged. They were detected in at least 45% of the samples: a 580 kb region at 1p34.2 -p34.3 and a 270 kb region at 1p11.2. We further defined the potential importance of these genomic amplifications by analysing the RNA expression of the genes in these regions with Affymetrix oligonucleotide arrays and semiquantitative reverse transcriptase -polymerase chain reaction. Our data revealed overexpression of the genes HEYL, HPCAL4, BMP8, IPT, and RLF, coinciding with genomic amplification.

show abstract

Chromosomal alterations in small cell lung cancer revealed by multicolour fluorescence in situ hybridization

Cited by 29 publications

References 16 publications

Establishment in Severe Combined Immunodeficiency Mice of Subrenal Capsule Xenografts and Transplantable Tumor Lines from a Variety of Primary Human Lung Cancers: Potential Models for Studying Tumor Progression–Related Changes

Establishment in Severe Combined Immunodeficiency Mice of Subrenal Capsule Xenografts and Transplantable Tumor Lines from a Variety of Primary Human Lung Cancers: Potential Models for Studying Tumor Progression–Related Changes

Integrative Genomic Analysis of Small-Cell Lung Carcinoma Reveals Correlates of Sensitivity to Bcl-2 Antagonists and Uncovers Novel Chromosomal Gains

Genomic and gene expression profiling of minute alterations of chromosome arm 1p in small-cell lung carcinoma cells

Contact Info

Product

Resources

About