Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction

The search for genetic damage in neoplastic cells now occupies a central place in cancer research. Diverse examples of such damage are in hand, and they in turn hint at biochemical explanations for neoplastic growth. The way may be open to solve the riddles of how normal cells govern their replication and why cancer cells do not.

https://science.sciencemag.org/content/sci/235/4786/305.full.pdf

The molecular genetics of cancer

Interest in the Ets proteins has grown enormously over the last decade. The v-ets oncogene was originally discovered as part of a fusion protein expressed by a transforming retrovirus (avian E26), and later shown to be transduced from a cellular gene. About 30 related proteins have now been found in species ranging from flies to humans, that resemble the vEts protein in the so-called 'ets domain'. The ets domain has been shown to be a DNA-binding domain, that specifically interacts with sequences containing the common core trinucleotide GGA. Furthermore, it is involved in protein-protein interactions with co-factors that help determine its biological activity. Many of the Ets-related proteins have been shown to be transcription activators, like other nuclear oncoproteins and anti-oncoproteins (Jun, Fos, Myb, Myc, Rel, p53, etc.). However, Ets-like proteins may have other functions, such as in DNA replication and a general role in transcription activation. Ets proteins have been implicated in regulation of gene expression during a variety of biological processes, including growth control, transformation, T-cell activation, and developmental programs in many organisms. Signals regulating cell growth are transmitted from outside the cell to the nucleus by growth factors and their receptors. G-proteins, kinases and transcription factors. We will discuss how several Ets-related proteins fit into this scheme, and how their activity is regulated both post- and pre-translationally. Loss of normal control is often associated with conversion to an oncoprotein. vEts has been shown to have different properties from its progenitor, which might explain how it has become oncogenic. Oncogene-related products have been implicated in the control of various developmental processes. Evidence is accumulating for a role for Ets family members in Drosophila development, Xenopus oocyte maturation, lymphocyte differentiation, and viral infectious cycles. An ultimate hope in studying transformation by oncoproteins is to understand how cells become cancerous in humans, which would lead to more effective treatments. vEts induces erythroblastosis in chicken. Cellular Ets-family proteins can be activated by proviral insertion in mice and, most interestingly, by chromosome translocation in humans. We are at the beginning of understanding the multiple facets of regulation of Ets activity. Future work on the Ets family promises to provide important insights into both normal control of growth and differentiation, and deregulation in illness.

https://febs.onlinelibrary.wiley.com/doi/epdf/10.1111/j.1432-1033.1993.tb19864.x

The Ets family of transcription factors

Identification of breakpoints in t(8;21) acute myelogenous leukemia and isolation of a fusion transcript, AML1/ETO, with similarity to Drosophila segmentation gene, runt.

Publisher Summary This chapter discusses the myc /IgH translocation. It considers the nature of the variant forms of the plasmacytoma and Burkitt translocations. The bcr–abl recombination that creates the Philadelphia chromosome is also described and its role in the development of chronic myeloid leukemia is considered. Three putative oncogenes— pvt-1, bcl-1, and bcE-2 —have been identified at the translocation junctions in lymphoid tumors by the molecular cloning of “aberrant” immunoglobulin gene rearrangements. Several other chromosomal abnormalities specific to particular lymphoid and myeloid neoplasms are assessed in the chapter for the possible involvement of oncogenes. The challenge for the future is not only to delineate the molecular basis for other translocations but also to identify the normal function of the genes involved. The frequent association of abnormalities involving band 11q23 in acute leukemias with monocytic differentiation suggests that they involve the alteration of a gene important in myelomonocytic differentiation. The recent localization of the metallothionein gene cluster to the band q22 of chromosome 16 raises intriguing questions regarding the chromosome abnormalities associated with acute myelomonocytic leukemia (AMML).

Activation of cellular oncogenes in hemopoietic cells by chromosome translocation.

Human probes identifying the cellular homologs of the v-ets gene, Hu-ets-1 and Hu-ets-2, and two panels of rodent-human cell hybrids were used to study specific translocations occurring in acute leukemias. The human ets-1 gene was found to translocate from chromosome 11 to 4 in the t(4;11)(q21;23), a translocation characteristic of a subtype of leukemia that represents the expansion of a myeloid/lymphoid precursor cell. Similarly, the human ets-2 gene was found to translocate from chromosome 21 to chromosome 8 in the t(8;21)(q22;q22), a nonrandom translocation commonly found in patients with acute myeloid leukemia with morphology M2 (AML-M2). Both translocations are associated with expression different from the expression in normal lymphoid cells of ets genes, raising the possibility that these genes play a role in the pathogenesis of these leukemias.

http://science.sciencemag.org/content/sci/231/4736/379.full.pdf

Hu-ets-1 and Hu-ets-2 genes are transposed in acute leukemias with (4;11) and 8;21) translocations

The human c-mos proto-oncogene is located on chromosome 8 at band q22, close to the breakpoint in the t(8;21) (q22;q22) chromosome rearrangement. This translocation is associated with acute myeloblastic leukemia, subgroup M2. The c-myc gene, another proto-oncogene, has been mapped to 8q24. The breakpoint at 8q22 separates these genes, as determined by in situ hybridization of c-mos and c-myc probes. The c-mos gene remains on the 8q-chromosome and the c-myc gene is translocated to the 21q+ chromosome. Southern blot analysis of DNA from bone marrow cells of four patients with this translocation showed no rearrangement of c-mos.

D. Patterson

Papers

Hu-ets-1 and Hu-ets-2 genes are transposed in acute leukemias with (4;11) and 8;21) translocations

The role of the c-mos gene in the 8;21 translocation in human acute myeloblastic leukemia.