A point mutation in the c-myc locus of a Burkitt lymphoma abolishes binding of a nuclear protein

A 20-base pair region in the first intron of the human c-myc gene was identified as the binding site of a nuclear protein. This binding site is mutated in five out of seven Burkitt lymphomas sequenced to date. To investigate the protein-recognition region in greater detail, the abnormal c-myc allele from a Burkitt lymphoma line (PA682) that carries a t(8;22) chromosomal translocation was used. A point mutation in the binding region of the PA682 c-myc DNA abolished binding of this nuclear protein. This protein may be an important factor for control of c-myc expression, and mutations in its recognition sequence may be associated with c-myc activation in many cases of Burkitt lymphoma.     

Avian v-myc replaces chromosomal translocation in murine plasmacytomagenesis

Deregulation of c-myc expression in association with chromosomal translocations occurs in over 95% of murine plasmacytomas, rat immunocytomas, and human Burkitt lymphomas. Infection with a murine retrovirus (J-3) containing an avian v-myc rapidly induced plasmacytomas in pristane-primed BALB/cAn mice. Only 17% of the induced plasmacytomas that were karyotyped showed the characteristic chromosomal translocations involving the c-myc locus. Instead, all of the translocation-negative tumors demonstrated characteristic J-3 virus integration sites that were actively transcribed. Thus, the high levels of v-myc expression have replaced the requirement for chromosomal translocation in plasmacytomagenesis and accelerated the process of transformation.     

Mapping of the human Blym-1 transforming gene activated in Burkitt lymphomas to chromosome 1

Blym-1, a transforming gene detected by transfection of NIH 3T3 cells with DNA from Burkitt lymphomas, was mapped to the short arm of chromosome 1 (1p32) by chromosomal in situ hybridization. The Blym-1 gene was not physically linked to the cellular myc oncogene or to any of the immunoglobulin gene loci implicated in the characteristic chromosomal translocations in Burkitt lymphoma.     

A common mechanism of chromosomal translocation in T- and B-cell neoplasia

The chromosomal breakpoint involved in the t(8;14)(q24;q11) chromosome translocation in the SKW-3 cell line, which directly involves the 3' flanking region of the c-myc gene, was cloned and sequenced. The breakpoint on chromosome 8 mapped to a position 3 kb 3' of c-myc while the chromosome 14 breakpoint occurred 36 kb 5' of the gene for the constant region of the alpha chain of the T-cell receptor (TCR). The translocation resulted in a precise rearrangement of sequences on chromosome 8 and what appears to be a functional J alpha segment on chromosome 14. Signal sequences for V-J joining occurred at the breakpoint positions on both chromosomes 14 and 8, suggesting that the translocation occurs during TCR gene rearrangement and that it is catalyzed by the enzymatic systems involved in V-J joining reactions. The involvement of c-myc in the translocation and the association of joining signals at the breakpoints provides a parallel to the situation observed in the translocations involving c-myc and the immunoglobulin loci in B-cell neoplasms and suggests that common mechanisms of translocation and oncogene deregulation are involved in B- and T-cell malignancies.     

Translocation and rearrangements of the c-myc oncogene locus in human undifferentiated B-cell lymphomas

The locus for the cellular myc (c-myc) oncogene in humans is located on the region of chromosome 8 that is translocated to chromosome 14 in cells from most undifferentiated B-cell lymphomas. It is shown in this study that the c-myc locus is rearranged in 5 out of 15 cell lines from patients with undifferentiated B-cell lymphomas, and that the rearrangement involves a region at the 5' side of an apparently intact c-myc gene. In at least three patients, this rearranged region appears to contain immunoglobulin heavy chain mu sequences that are located on chromosome 14. The data indicate that this region contains the crossover point between chromosomes 8 and 14. The break point can occur at different positions on both chromosomes among individual cell lines.     

Gene for alpha-chain of human T-cell receptor: location on chromosome 14 region involved in T-cell neoplasms

A human complementary DNA clone specific for the alpha-chain of the T-cell receptor and a panel of rodent X human somatic cell hybrids were used to map the alpha-chain gene to human chromosome 14 in a region proximal to the immunoglobulin heavy chain locus. Analysis by means of in situ hybridization of human metaphase chromosomes served to further localize the alpha-chain gene to region 14q11q12, which is consistently involved in translocations and inversions detectable in human T-cell leukemias and lymphomas. Thus, the locus for the alpha-chain T-cell receptor may participate in oncogene activation in T-cell tumors.     

A glycolipid antigen associated with Burkitt lymphoma defined by a monoclonal antibody

The antigen defined by a rat monoclonal antibody directed to a Burkitt lymphoma cell line was identified as globotriaosylceramide [Gal alpha (1 leads to 4)-Gal beta (1 leads to 4)-Glc beta (1 leads to 1)-ceramide]. The antibody demonstrated a strict steric specificity since it did not react with globoisotriaosylceramide [Gal alpha (1 leads to 3)-Gal beta (1 leads to 4)-Glc beta (1 leads to 1)-ceramide], the positional isomer of the antigen associated with the Burkitt lymphoma. Chemical analysis of various Burkitt lymphoma cell lines revealed that the Burkitt lymphoma cells contained more than 100 times as much of the glycolipid antigen as was found in other human lymphoma and leukemia cell lines.     

基于RNA-seq的百萨偃麦草染色体特异分子标记开发与应用

【目的】百萨偃麦草（Thinopyrum bessarabicum Löve, 2n = 2x = 14, JJ或E^bE^b）是小麦改良的重要亲缘物种,开发染色体特异分子标记对于加快其有利基因向小麦中的转移和应用有重要意义。【方法】利用百萨偃麦草分蘖期叶片RNA-seq获得的EST序列与节节麦D基因组序列进行比对,鉴定出4 957条没有相似性的序列作为筛选百萨偃麦草特异序列的基础序列。从这些基础序列中随机选择部分序列设计EST-PCR引物507对,通过在普通小麦中国春、百萨偃麦草和中国春-百萨偃麦草双二倍体中的扩增分析,筛选出百萨偃麦草基因组特异标记,然后在已经选育出的8个小麦-百萨偃麦草异染色体系中进行染色体定位,并探讨这些标记在小麦染色体工程中的应用潜力;根据谷类作物的共线性,以百萨偃麦草EST序列设计共线性引物100对,并比较这些引物的扩增和定位结果。【结果】在开发的507对引物中,204对（40.2%）在百萨偃麦草和中国春-百萨偃麦草双二倍体中具有特异扩增,多态率远高于利用小麦（12%）和百萨偃麦草（14%）EST设计的234对共线性引物产生的多态率,建立了高效开发小麦亲缘物种特异标记的新方法;利用8个中国春-百萨偃麦草异染色体系,共定位了198个百萨偃麦草特异标记,分别位于染色体1J（31）、2JS（15）、2JL（26）、3JS（20）、4JS（12）、4JL（12）、5J（27）、6JS（13）、6JL（22）和7JS（20）,其中189个是根据百萨偃麦草转录组序列设计;利用定位于1J和6J的特异标记确定了4个易位系的染色体身份,其中1个涉及1J的大片段易位,2个涉及6JS的不同区段易位,1个为小片段中间插入易位;利用这些易位系,将30个1J和12个6J特异标记分别定位于2个物理区段。【结论】通过RNA-seq结合与小麦基因组序列比对可以获得小麦亲缘物种相对特异的EST序列并据此开发引物,建立了开发外源染色体特异标记的新方法,开发的标记可应用于小麦异易位系鉴定和缺失物理图谱的绘制。