Genes overexpressed in different human solid cancers exhibit different tissue-specific expression profiles

We have analyzed gene expression in different normal human tissues and different types of solid cancers derived from these tissues. The cancers analyzed include brain (astrocytoma and glioblastoma), breast, colon, endometrium, kidney, liver, lung, ovary, prostate, skin, and thyroid cancers. Comparing gene expression in each normal tissue to 12 other normal tissues, we identified 4,917 tissue-selective genes that were selectively expressed in different normal tissues. We also identified 2,929 genes that are overexpressed at least 4-fold in the cancers compared with the normal tissue from which these cancers were derived. The overlap between these two gene groups identified 1,340 tissue-selective genes that are overexpressed in cancers. Different types of cancers, including different brain cancers arising from the same lineage, showed differences in the tissue-selective genes they overexpressed. Melanomas overexpressed the highest number of brain-selective genes and this may contribute to melanoma metastasis to the brain. Of all of the genes with tissue-selective expression, those selectively expressed in testis showed the highest frequency of genes that are overexpressed in at least two types of cancer. However, colon and prostate cancers did not overexpress any testis-selective gene. Nearly all of the genes with tissue-selective expression that are overexpressed in cancers showed selective expression in tissues different from the cancers' tissue of origin. Cancers aberrantly expressing such genes may acquire phenotypic alterations that contribute to cancer cell viability, growth, and metastasis.

[1]  J. Lotem,et al.  Epigenetics and the plasticity of differentiation in normal and cancer stem cells , 2006, Oncogene.

[2]  S. Horvath,et al.  Gene Expression Profiling of Gliomas Strongly Predicts Survival , 2004, Cancer Research.

[3]  Jeffrey T. Chang,et al.  Oncogenic pathway signatures in human cancers as a guide to targeted therapies , 2006, Nature.

[4]  L. Giudice,et al.  Molecular phenotyping of human endometrium distinguishes menstrual cycle phases and underlying biological processes in normo-ovulatory women. , 2006, Endocrinology.

[5]  Terence P. Speed,et al.  A comparison of normalization methods for high density oligonucleotide array data based on variance and bias , 2003, Bioinform..

[6]  Kay Nieselt,et al.  Progression-specific genes identified by expression profiling of matched ductal carcinomas in situ and invasive breast tumors, combining laser capture microdissection and oligonucleotide microarray analysis. , 2006, Cancer research.

[7]  C. Sotiriou,et al.  Molecular profiling of head and neck tumors , 2004, Current opinion in oncology.

[8]  G. Sherlock,et al.  The prognostic role of a gene signature from tumorigenic breast-cancer cells. , 2007, The New England journal of medicine.

[9]  H. Sasaki,et al.  Gene expression profiling identifies a set of transcripts that are up-regulated inhuman testicular seminoma. , 2004, DNA research : an international journal for rapid publication of reports on genes and genomes.

[10]  Thomas D. Wu,et al.  Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. , 2006, Cancer cell.

[11]  Lloyd J. Old,et al.  Cancer/testis antigens, gametogenesis and cancer , 2005, Nature Reviews Cancer.

[12]  Doron Lancet,et al.  Genome-wide midrange transcription profiles reveal expression level relationships in human tissue specification , 2005, Bioinform..

[13]  A. Simpson,et al.  The cancer/testis genes: review, standardization, and commentary. , 2004, Cancer immunity.

[14]  W. Cleveland,et al.  Locally Weighted Regression: An Approach to Regression Analysis by Local Fitting , 1988 .

[15]  D. Bigner,et al.  Recent advances in the treatment of malignant astrocytoma. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  S. Batalov,et al.  A gene atlas of the mouse and human protein-encoding transcriptomes. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[17]  D. Carrasco,et al.  Identification of genes modulated in multiple myeloma using genetically identical twin samples. , 2004, Blood.

[18]  H. Aburatani,et al.  Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. , 2005, Genomics.

[19]  A. Olshen,et al.  Down-regulation of stem cell genes, including those in a 200-kb gene cluster at 12p13.31, is associated with in vivo differentiation of human male germ cell tumors. , 2006, Cancer research.

[20]  Chan Zeng,et al.  Human lung project: evaluating variance of gene expression in the human lung. , 2006, American journal of respiratory cell and molecular biology.

[21]  Paola Pisani,et al.  Genetic Pathways to Glioblastoma , 2004, Cancer Research.

[22]  B. Czepulkowski,et al.  Frequent expression of HAGE in presentation chronic myeloid leukaemias , 2002, Leukemia.

[23]  M. Middleton,et al.  Brain metastases in melanoma: a European perspective. , 2002, Seminars in oncology.

[24]  M. Cotreau,et al.  Molecular classification of Crohn's disease and ulcerative colitis patients using transcriptional profiles in peripheral blood mononuclear cells. , 2006, The Journal of molecular diagnostics : JMD.

[25]  David Edwards,et al.  Non-linear Normalization and Background Correction in One-channel CDNA Microarray Studies , 2003, Bioinform..

[26]  Lawrence D True,et al.  Transcriptomes of human prostate cells , 2006, BMC Genomics.

[27]  Koji Yoshimoto,et al.  Primary Glioblastomas Express Mesenchymal Stem-Like Properties , 2006, Molecular Cancer Research.

[28]  Shenhua Xu,et al.  Gene expression profile differences in gastric cancer, pericancerous epithelium and normal gastric mucosa by gene chip. , 2005, World journal of gastroenterology.

[29]  Shridar Ganesan,et al.  X chromosomal abnormalities in basal-like human breast cancer. , 2006, Cancer cell.

[30]  P. Hevezi,et al.  Gene expression analyses reveal molecular relationships among 20 regions of the human CNS , 2006, Neurogenetics.

[31]  E. Lander,et al.  Gene expression correlates of clinical prostate cancer behavior. , 2002, Cancer cell.

[32]  Eleanor Woodward,et al.  Microarray analysis of tumour antigen expression in presentation acute myeloid leukaemia. , 2005, Biochemical and biophysical research communications.

[33]  Dennis B. Troup,et al.  NCBI GEO: mining tens of millions of expression profiles—database and tools update , 2006, Nucleic Acids Res..

[34]  Patrik Edén,et al.  Molecular signatures in childhood acute leukemia and their correlations to expression patterns in normal hematopoietic subpopulations. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[35]  John Quackenbush.  Microarray data normalization and transformation , 2002, Nature Genetics.

[36]  E. Domany,et al.  Induction in myeloid leukemic cells of genes that are expressed in different normal tissues. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[37]  E. Domany,et al.  Human cancers overexpress genes that are specific to a variety of normal human tissues. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[38]  Eytan Domany,et al.  Relationship of gene expression and chromosomal abnormalities in colorectal cancer. , 2006, Cancer research.

[39]  Lingli Wang,et al.  A Transcriptional Profile of Aging in the Human Kidney , 2004, PLoS biology.

[40]  Yixin Wang,et al.  Novel Genes Associated with Malignant Melanoma but not Benign Melanocytic Lesions , 2005, Clinical Cancer Research.

[41]  S. Green,et al.  Glioblastoma multiforme and anaplastic astrocytoma pathologic criteria and prognostic implications , 1985, Cancer.