The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile.

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The cancer genome atlas pan-cancer analysis project

The Cancer Genome Atlas Pan-Cancer analysis project

Transfection of embryo fibroblasts by a human ras oncogene does not convert them into tumour cells unless the fibroblasts are established and immortalized before transfection. The embryo fibroblasts become tumorigenic if a second oncogene such as a viral or cellular myc gene or the gene for the polyoma large-T antigen is introduced together with the ras gene.

Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes.

Transgenic mice bearing the cellular myc oncogene coupled to the immunoglobulin mu or kappa enhancer frequently develop a fatal lymphoma within a few months of birth. Since the tumours represent represent both immature and mature B lymphocytes, constitutive c-myc expression appears to be highly leukaemogenic at several stages of B-cell maturation. These myc mice should aid study of lymphoma development, B-cell ontogeny and immunoglobulin regulation.

The c- myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice

https://www.cell.com/cell/pdf/0092-8674(82)90409-3.pdf

Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome.

Proviruses of avian leukosis virus (ALV) are located in the vicinity of a putative cellular oncogene (c-myc) in ALV-induced bursal lymphomas. Enhanced expression of c-myc occurs in association with proviruses found in any of three configurations: (I) on the 5′ side (‘upstream’) of c-myc in the same transcriptional orientation; (II) on the 3′ side (‘downstream’) of c-myc in the same orientation; (III) upstream, in the transcriptional orientation opposite to that of c-myc. Thus, activation of adjacent cellular genes by retroviral DNA can involve mechanisms other than provision of a transcriptional promoter.

Multiple arrangements of viral DNA and an activated host oncogene in bursal lymphomas

Analysis of avian leukosis virus DNA and RNA in bursal tumors: Viral gene expression is not required for maintenance of the tumor state

Heterogeneity of genetic loci in chickens: analysis of endogenous viral and nonviral genes by cleavage of DNA with restriction endonucleases

DNA intermediates in the replication of retroviruses are structurally (and perhaps functionally) related to transposable elements.

Bursal lymphomas induced in chickens by avian leukosis viruses (ALVs) harbor proviral insertions that augment expression of an adjacent cellular oncogene, c-myc. To analyze such insertionally mutagenized c-myc genes in greater detail, we isolated molecular clones from two indepen- dent tumors. Precise proviral integration has occurred within the transcribed region of the c-myc gene in both mutant alleles. The proviruses bear different internal deletions that preclude the expression of the gag, pol, and env genes. The c-myc gene from bursal lymphoma LL4 contains a single copy of an ALV long terminal repeat (LTR), presumably the product of ho- mologous recombination between LTRs at the'ends of a nor- mal provirus; the "solo" LTR is positioned in the correct ori- entation to act as a promoter for the c-myc gene. Bursal lym- phoma LL3 contains an ALV provirus positioned upstream in the opposite transcriptional orientation to the coding exons of c-myc and deleted from a site within the leader region into the gag gene. In addition, the nucleotide sequence of the c-myc gene from tumor LL3 differs from the published sequence of the normal c-myc coding region at 3 positions of 180 deter- mined. One of these changes, a silent nucleotide transition, is documented as a somatic mutation by restriction endonuclease mapping. It is flanked by two other candidate tumor-specific point mutations, one of which predicts an amino acid replace- ment, Pro -* Thr at position 63. Thus, additional lesions that may affect the expression of viral genes and the quantity and nature of the putative c-myc gene product occur in provirally mutated c-myc alleles and may contribute to tumor progres- sion.

Proviral deletions and oncogene ba mutagenized c-myc alleles may coni of avian bursal tumors (somatic mutation/homologous recombination/transposable elements)

Gregory S. Payne

Papers

Multiple arrangements of viral DNA and an activated host oncogene in bursal lymphomas

Analysis of avian leukosis virus DNA and RNA in bursal tumors: Viral gene expression is not required for maintenance of the tumor state

Heterogeneity of genetic loci in chickens: analysis of endogenous viral and nonviral genes by cleavage of DNA with restriction endonucleases

DNA intermediates in the replication of retroviruses are structurally (and perhaps functionally) related to transposable elements.

Proviral deletions and oncogene ba mutagenized c-myc alleles may coni of avian bursal tumors (somatic mutation/homologous recombination/transposable elements)