Cells of origin in cancer

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Jamieson, C. H. et al. Granulocyte–macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. N. Engl. J. Med. 351, 657–667 (2004). The first functional evidence that cells of origin and cancer-propagating cells in a given malignancy are likely to be distinct.

Hope, K. J., Jin, L. & Dick, J. E. Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nature Immunol. 5, 738–743 (2004).

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Wei, J. et al. Microenvironment determines lineage fate in a human model of MLL-AF9 leukemia. Cancer Cell 13, 483–495 (2008).

Hong, D. et al. Initiating and cancer-propagating cells in TEL-AML1-associated childhood leukemia. Science 319, 336–339 (2008).

Huntly, B. J. et al. MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors. Cancer Cell 6, 587–596 (2004).

Krivtsov, A. V. et al. Transformation from committed progenitor to leukaemia stem cell initiated by MLL–AF9. Nature 442, 818–822 (2006).

Cozzio, A. et al. Similar MLL-associated leukemias arising from self-renewing stem cells and short-lived myeloid progenitors. Genes Dev. 17, 3029–3035 (2003).

Drynan, L. F. et al. Mll fusions generated by Cre-loxP-mediated de novo translocations can induce lineage reassignment in tumorigenesis. EMBO J. 24, 3136–3146 (2005).

Chen, W. et al. Malignant transformation initiated by Mll-AF9: gene dosage and critical target cells. Cancer Cell 13, 432–440 (2008). This study highlights the importance of gene dosage when assessing the effects of oncogene expression in candidate cells of origin.

McCormack, M. P. et al. The Lmo2 oncogene initiates leukemia in mice by inducing thymocyte self-renewal. Science 327, 879–883 (2010).

Akala, O. O. et al. Long-term haematopoietic reconstitution by Trp53−/−p16Ink4a−/−p19Arf−/− multipotent progenitors. Nature 453, 228–232 (2008).

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Barker, N. et al. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 457, 608–611 (2009). Using lineage-tracing studies, this paper demonstrates that colonic stem cells can act as the cell of origin for colon cancer. See also references 37 and 38.

Zhu, L. et al. Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation. Nature 457, 603–607 (2009).

Sangiorgi, E. & Capecchi, M. R. Bmi1 is expressed in vivo in intestinal stem cells. Nature Genet. 40, 915–920 (2008).

Barker, N. et al. Lgr5+ve stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro . Cell Stem Cell 6, 25–36 (2010).

Holland, E. C. et al. Combined activation of Ras and Akt in neural progenitors induces glioblastoma formation in mice. Nature Genet. 25, 55–57 (2000).

Alcantara Llaguno, S. et al. Malignant astrocytomas originate from neural stem/progenitor cells in a somatic tumor suppressor mouse model. Cancer Cell 15, 45–56 (2009).

Marumoto, T. et al. Development of a novel mouse glioma model using lentiviral vectors. Nature Med. 15, 110–116 (2009).

Merkle, F. T., Mirzadeh, Z. & Alvarez-Buylla, A. Mosaic organization of neural stem cells in the adult brain. Science 317, 381–384 (2007).

Jacques, T. S. et al. Combinations of genetic mutations in the adult neural stem cell compartment determine brain tumour phenotypes. EMBO J. 29, 222–235 (2010).

Wang, Y. et al. Expression of mutant p53 proteins implicates a lineage relationship between neural stem cells and malignant astrocytic glioma in a murine model. Cancer Cell 15, 514–526 (2009).

Bachoo, R. M. et al. Epidermal growth factor receptor and Ink4a/Arf: convergent mechanisms governing terminal differentiation and transformation along the neural stem cell to astrocyte axis. Cancer Cell 1, 269–277 (2002).

Bruggeman, S. W. et al. Bmi1 controls tumor development in an Ink4a/Arf-independent manner in a mouse model for glioma. Cancer Cell 12, 328–341 (2007).

Schuller, U. et al. Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma. Cancer Cell 14, 123–134 (2008). This study demonstrates that descendants of stem cells can act as crucial cellular targets of transformation. See also reference 49.

Yang, Z. J. et al. Medulloblastoma can be initiated by deletion of Patched in lineage-restricted progenitors or stem cells. Cancer Cell 14, 135–145 (2008).

Sutter, R. et al. Cerebellar stem cells act as medulloblastoma-initiating cells in a mouse model and a neural stem cell signature characterizes a subset of human medulloblastomas. Oncogene 29, 1845–1856 (2010).

Gibson, P. et al. Subtypes of medulloblastoma have distinct developmental origins. Nature 468, 1095–1098 (2010).

Joseph, N. M. et al. The loss of Nf1 transiently promotes self-renewal but not tumorigenesis by neural crest stem cells. Cancer Cell 13, 129–140 (2008).

Zheng, H. et al. Induction of abnormal proliferation by nonmyelinating Schwann cells triggers neurofibroma formation. Cancer Cell 13, 117–128 (2008).

Wang, X. et al. A luminal epithelial stem cell that is a cell of origin for prostate cancer. Nature 461, 495–500 (2009). This report establishes a new luminal stem cell as a target of prostate carcinogenesis and indicates a hierarchy of stem cells in this tissue.

Leong, K. G., Wang, B. E., Johnson, L. & Gao, W. Q. Generation of a prostate from a single adult stem cell. Nature 456, 804–808 (2008).

Ma, X. et al. Targeted biallelic inactivation of Pten in the mouse prostate leads to prostate cancer accompanied by increased epithelial cell proliferation but not by reduced apoptosis. Cancer Res. 65, 5730–5739 (2005).

Korsten, H., Ziel-van der Made, A., Ma, X., van der Kwast, T. & Trapman, J. Accumulating progenitor cells in the luminal epithelial cell layer are candidate tumor initiating cells in a Pten knockout mouse prostate cancer model. PLoS ONE 4, e5662 (2009).

Mulholland, D. J. et al. Lin−Sca-1+CD49fhigh stem/progenitors are tumor-initiating cells in the Pten-null prostate cancer model. Cancer Res. 69, 8555–8562 (2009).

Lawson, D. A. et al. Basal epithelial stem cells are efficient targets for prostate cancer initiation. Proc. Natl Acad. Sci. USA 107, 2610–2615 (2010).

Goldstein, A. S., Huang, J., Guo, C., Garraway, I. P. & Witte, O. N. Identification of a cell-of-origin for human prostate cancer. Science 329, 568–571 (2010). This study demonstrates through transduction of isolated cell subsets that basal stem/progenitor cells are an important target cell.

Foulkes, W. D. BRCA1 functions as a breast stem cell regulator. J. Med. Genet. 41, 1–5 (2004).

Turner, N., Tutt, A. & Ashworth, A. Hallmarks of 'BRCAness' in sporadic cancers. Nature Rev. Cancer 4, 814–819 (2004).

Molyneux, G. et al. BRCA1 basal-like breast cancers originate from luminal epithelial progenitors not from basal stem cells. Cell Stem Cell 7, 403–417 (2010). This study provides in vivo functional evidence that luminal progenitors rather than basal cells are an important target in the genesis of BRCA1-associated breast tumours.

Liu, S. et al. BRCA1 regulates human mammary stem/progenitor cell fate. Proc. Natl Acad. Sci. USA 105, 1680–1685 (2008).

Bouras, T. et al. Notch signaling regulates mammary stem cell function and luminal cell-fate commitment. Cell Stem Cell 3, 429–441 (2008).

Lee, C. W. et al. A functional Notch–survivin gene signature in basal breast cancer. Breast Cancer Res. 10, R97 (2008).

Vaillant, F. et al. The mammary progenitor marker CD61/β3 integrin identifies cancer stem cells in mouse models of mammary tumorigenesis. Cancer Res. 68, 7711–7717 (2008).

Prat, A. et al. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res. 12, R68 (2010).

Gidekel Friedlander, S. Y. et al. Context-dependent transformation of adult pancreatic cells by oncogenic K-Ras. Cancer Cell 16, 379–389 (2009).

De La, O. J. et al. Notch and Kras reprogram pancreatic acinar cells to ductal intraepithelial neoplasia. Proc. Natl Acad. Sci. USA 105, 18907–18912 (2008).

Habbe, N. et al. Spontaneous induction of murine pancreatic intraepithelial neoplasia (mPanIN) by acinar cell targeting of oncogenic Kras in adult mice. Proc. Natl Acad. Sci. USA 105, 18913–18918 (2008).

Youssef, K. K. et al. Identification of the cell lineage at the origin of basal cell carcinoma. Nature Cell Biol. 12, 299–305 (2010).

Owens, D. M. & Watt, F. M. Contribution of stem cells and differentiated cells to epidermal tumours. Nature Rev. Cancer 3, 444–451 (2003).

Bonnet, D. & Dick, J. E. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nature Med. 3, 730–737 (1997). The first report indicating that early stem/progenitor cells are targeted for transformation in AML.

Ricci-Vitiani, L. et al. Identification and expansion of human colon-cancer-initiating cells. Nature 445, 111–115 (2007).

O'Brien, C. A., Pollett, A., Gallinger, S. & Dick, J. E. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445, 106–110 (2007).

Kim, C. F. et al. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 121, 823–835 (2005).

Curtis, S. J. et al. Primary tumor genotype is an important determinant in identification of lung cancer propagating cells. Cell Stem Cell 7, 127–133 (2010).

Zhang, L. et al. Chemoprevention of colorectal cancer by targeting APC-deficient cells for apoptosis. Nature 464, 1058–1061 (2010).

Martin, S. A. et al. DNA polymerases as potential therapeutic targets for cancers deficient in the DNA mismatch repair proteins MSH2 or MLH1. Cancer Cell 17, 235–248 (2010).

Forbes, J. F. et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol. 9, 45–53 (2008).

Asselin-Labat, M. L. et al. Control of mammary stem cell function by steroid hormone signalling. Nature 465, 798–802 (2010).

Ashworth, A. Drug resistance caused by reversion mutation. Cancer Res. 68, 10021–10023 (2008).

Tutt, A. et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet 376, 235–244 (2010).

Lindberg, N., Kastemar, M., Olofsson, T., Smits, A. & Uhrbom, L. Oligodendrocyte progenitor cells can act as cell of origin for experimental glioma. Oncogene 28, 2266–2275 (2009).