Chromosome abnormalities in 10 lung cancer cell lines of the NCI-H series analyzed with spectral karyotyping.

The karyotypes of 10 lung cancer cell lines of the NCI-H series were analyzed with spectral karyotyping (SKY): 7 non-small lung cancer (NSCLC) lines and 3 small cell lung cancer (SCLC) lines. Modal chromosome number ranged from 42 (NCI-H2171) to 72 (NCI-H2126). All lines showed at least six structural abnormalities, and most had amplifications visible as double minutes or homogeneously staining regions (HSRs). Four reciprocal translocations were found: t(1;17)(p10;p10) in NCI-H82, t(3;6)(q24;q21) and t(12;17)(p10;p10) in NCI-H2009, and a complex t(2;6) in NCI-H1437. NCI-H1770 had a striking HSR containing many copies of the NMYC region. Karyotypes showed a wide range of relationship between numerical and structural change. Two of the lines showed little numerical change but many structural rearrangements (NCI-H209 with mode 46, but 12 rearrangements, and NCI-H2009 with mode 48 but 27 rearrangements). A second group had karyotypes that appeared to have evolved by unbalanced translocation leading to proportionate loss of chromosomes, with or without endoreduplication. In other lines, notably NCI-H2122, the structurally abnormal chromosomes appeared to have been added to a near-diploid karyotype. The karyotypes contribute to a full genomic characterization of these lines, almost all of which have matching normal lymphoblastoid cell lines.

[1]  J. Minna,et al.  A nonrandom chromosomal abnormality, del 3p(14-23), in human small cell lung cancer (SCLC). , 1982, Cancer genetics and cytogenetics.

[2]  J. Testa,et al.  Chromosomal imbalances in human lung cancer , 2002, Oncogene.

[3]  P. Meltzer,et al.  Specific chromosomal aberrations and amplification of the AIB1 nuclear receptor coactivator gene in pancreatic carcinomas. , 1999, The American journal of pathology.

[4]  R. Makuch,et al.  myc family DNA amplification in small cell lung cancer patients' tumors and corresponding cell lines. , 1988, Cancer research.

[5]  D. Ledbetter,et al.  Multicolor Spectral Karyotyping of Human Chromosomes , 1996, Science.

[6]  B. Johansson,et al.  Fusion genes and rearranged genes as a linear function of chromosome aberrations in cancer , 2004, Nature Genetics.

[7]  L Cawkwell,et al.  Chromosomal analysis of non-small-cell lung cancer by multicolour fluorescent in situ hybridisation , 2004, British Journal of Cancer.

[8]  P. Edwards,et al.  Non-random chromosomal rearrangements in pancreatic cancer cell lines identified by spectral karyotyping. , 2001 .

[9]  J. Weinstein,et al.  Karyotypic complexity of the NCI-60 drug-screening panel. , 2003, Cancer research.

[10]  A. Gazdar,et al.  Cell culture methods for the establishment of the NCI series of lung cancer cell lines , 1996, Journal of cellular biochemistry. Supplement.

[11]  C. D. Edwards,et al.  Reciprocal Rb inactivation and p16INK4 expression in primary lung cancers and cell lines. , 1995, Cancer research.

[12]  Carlos Caldas,et al.  A Recurrent Chromosome Breakpoint in Breast Cancer at the NRG1/Neuregulin 1/Heregulin Gene , 2004, Cancer Research.

[13]  F. Mitelman,et al.  Recurrent chromosome aberrations in cancer. , 2000, Mutation research.

[14]  M. Fishbein,et al.  A candidate tumor suppressor gene, H37, from the human lung cancer tumor suppressor locus 3p21.3. , 2002, Cancer research.

[15]  A. Stock,et al.  A molecular cytogenetic study of chromosome 3 rearrangements in small cell lung cancer: consistent involvement of chromosome band 3q13.2. , 1999, Cancer genetics and cytogenetics.

[16]  J. Rowley,et al.  Chromosome translocations: dangerous liaisons revisited , 2001, Nature Reviews Cancer.

[17]  B. Dutrillaux Pathways of chromosome alteration in human epithelial cancers. , 1995, Advances in cancer research.

[18]  F. Bertucci,et al.  Reciprocal translocations in breast tumor cell lines: Cloning of a t(3;20) that targets the FHIT gene , 2002, Genes, chromosomes & cancer.

[19]  P. Edwards,et al.  Spectral karyotyping suggests additional subsets of colorectal cancers characterized by pattern of chromosome rearrangement , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[20]  M. Lind,et al.  Chromosomal alterations in small cell lung cancer revealed by multicolour fluorescence in situ hybridization , 2002, International journal of cancer.

[21]  B. Dutrillaux,et al.  Breast cancer genetic evolution: I. Data from cytogenetics and DNA content , 1991, Breast Cancer Research and Treatment.

[22]  P. Edwards,et al.  A recurrent chromosome translocation breakpoint in breast and pancreatic cancer cell lines targets the neuregulin/NRG1 gene , 2003, Genes, chromosomes & cancer.

[23]  J. Testa,et al.  Molecular implications of recurrent cytogenetic alterations in human small cell lung cancer. , 1993, Cancer detection and prevention.

[24]  J. Minna,et al.  NCI series of cell lines: An historical perspective , 1996, Journal of cellular biochemistry. Supplement.

[25]  D. Gisselsson,et al.  Statistical dissection of cytogenetic patterns in lung cancer reveals multiple modes of karyotypic evolution independent of histological classification. , 2004, Cancer genetics and cytogenetics.

[26]  B. Dutrillaux,et al.  Existence of two distinct processes of chromosomal evolution in near-diploid colorectal tumors. , 1988, Cancer genetics and cytogenetics.

[27]  D. Bell,et al.  Advances in the analysis of chromosome alterations in human lung carcinomas. , 1997, Cancer genetics and cytogenetics.

[28]  C. Larsson,et al.  Chromosomal alterations in 15 breast cancer cell lines by comparative genomic hybridization and spectral karyotyping , 2000, Genes, chromosomes & cancer.

[29]  J. Rowley,et al.  The critical role of chromosome translocations in human leukemias. , 1998, Annual review of genetics.

[30]  D. Ward,et al.  Karyotyping human chromosomes by combinatorial multi-fluor FISH , 1996, Nature Genetics.

[31]  A Kuzucu,et al.  Cytogenetic findings in thirty lung carcinoma patients. , 1998, Cancer genetics and cytogenetics.

[32]  M. Tsao,et al.  Molecular cytogenetic analysis of non-small cell lung carcinoma by spectral karyotyping and comparative genomic hybridization. , 2001, Cancer genetics and cytogenetics.

[33]  C Caldas,et al.  Molecular cytogenetic analysis of breast cancer cell lines , 2000, British Journal of Cancer.

[34]  N E Morton,et al.  Parameters of the human genome. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[35]  R. Eils,et al.  Analysis of Chromosomal Alterations in Non-Small Cell Lung Cancer by Multiplex-FISH, Comparative Genomic Hybridization, and Multicolor Bar Coding , 2000, Laboratory Investigation.

[36]  B. Gunawan,et al.  Molecular cytogenetic analysis of two primary squamous cell carcinomas of the lung using multicolor fluorescence in situ hybridization , 2001, Virchows Archiv.

[37]  J. Minna,et al.  Focus on lung cancer. , 2002, Cancer cell.