Isolation, Characterization, and Organ-Specific Expression of Two Novel Human Zinc Finger Genes Related to theDrosophilaGenespalt

Kohlhase, Jürgen; Schuh, Reinhard; Dowe, G. H. C.; Kühnlein, Ronald P.; Jäckle, Herbert; Schroêder, B.; Schulz‐Schaeffer, Walter; Kretzschmar, Hans A.; Köhler, Angelika; Müller, Ulrich; Raab-Vetter, M.; Burkhardt, Elke; Engel, Wolfgang; Stick, Reimer

doi:10.1006/geno.1996.0631

Cited by 138 publications

(144 citation statements)

References 7 publications

(15 reference statements)

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“…Therefore, early detection with accurate methods is significantly required (Cenitagoya et al, 1998). The SALL gene family, including four members (SALL1 to SALL4), was initially cloned based on DNA sequence homology to the Drosophila gene spalt (sal) (Kohlhase et al, 1996). Sal is an essential homeotic gene for the development of the fly .…”

Section: Introductionmentioning

confidence: 99%

ZNF797 plays an oncogenic role in gastric cancer

et al. 2014

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ABSTRACT. Human cancer cells resemble stem cells in expression signatures leading them to share some features, most notably, selfrenewal. A complex network of transcription factors and signaling molecules are required for continuation of this trait. ZNF797 (SALL4) is a zinc finger transcriptional activator crucial for maintenance of self-renewal in stem cells; however, its expression level has not yet been elucidated in gastric tumor cells. Its expression was analyzed to determine this level and probable clinicopathological consequences. SALL4 expression in fresh tumor and distant tumor-free tissues from 46 colorectal samples was compared by real-time polymerase chain reaction. Greater than a 2-fold increase in SALL4 expression was detected in 89.5% of tumors vs normal related tissues. SALL4 expression was significantly correlated with tumor cell metastasis to lymph nodes, especially in moderately differentiated tumor samples (P < 0.05). Furthermore, higher levels of SALL4 mRNA expression were significantly associated with younger patients with tumor cells in stages I and II (P < 0.05). These results indicate a relationship between SALL4 expression and tumor cell metastasis to lymph nodes and consequent progression of tumors to advanced stages III and IV. Along with the promising evidence of its role in self-renewal in various cancers, SALL4 is introduced as a potentially interesting therapeutic target to reverse a number of aberrations that promote gastric tumor development and maintenance. This result may lead to new approaches for cancer therapy.

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Section: Introductionmentioning

confidence: 99%

ZNF797 plays an oncogenic role in gastric cancer

et al. 2014

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“…Unexpectedly, these Sall1 knock-out mice did not show any phenotype in the heterozygous situation, and the homozygous mutants had only bilateral renal agenesis or severely hypoplastic kidneys with no preserved renal function (the same phenotype was observed in a knock-out mouse constructed by the authors group on two different genetic backgrounds; Kohlhase J, unpublished data). As an alternative explanation for the pathogenesis of TBS it was assumed that truncating SALL1 mutations could lead to the TBS phenotype by a dominant-negative action, with truncated proteins interfering with nuclear transport of the wild type proteins (Sweetman et al, 2003) resulting from dimerization of wild type and mutant proteins mediated by the evolutionarily highly conserved glutamine-rich domain within the aminoterminal part of all known SAL-like proteins (Buck et al, 2000;Farrell and Munsterberg, 2000;Farrell et al, 2001;Hollemann et al, 1996;Kohlhase et al, 2000;Kohlhase et al, 1999a;Kohlhase et al, 1996;Köster et al, 1997;Kühnlein et al, 1994;Onuma et al, 1999;Ott et al, 1996). McLeskey Kiefer et al created a transgenic mouse harboring a "typical" TBS-mutation within the Sall1 gene in order to mimic the molecular defect in human patients.…”

Section: Introductionmentioning

confidence: 99%

Detection of heterozygousSALL1 deletions by quantitative real time PCR proves the contribution of aSALL1 dosage effect in the pathogenesis of Townes-Brocks syndrome

et al. 2006

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Townes-Brocks syndrome (TBS) is an autosomal dominantly inherited disordercharacterized by ear, anal, limb, and renal malformations, and results from mutations in the gene SALL1. All SALL1 mutations previously found in TBS patients create preterminal termination codons. In accordance with the findings of pericentric inversions or balanced translocations, TBS was initially assumed to be caused by SALL1 haploinsufficiency. This assumption was strongly contradicted by a Sall1 mouse knock-out, because neither heteronor homozygous knock-out mutants displayed a TBS-like phenotype. A different mouse mutant mimicking the human SALL1 mutations, however, showed a TBS-like phenotype in the heterozygous situation, suggesting a dominant-negative action of the mutations causing TBS. We applied quantitative real time PCR to detect and map SALL1 deletions in 240 patients with the clinical diagnosis of TBS, who were negative for SALL1 mutations. Deletions were found in three families. In the first family, a 75 kb deletion including all SALL1 exons had been inherited by two siblings from their father. A second, sporadic patient carried a de novo 1.9-2.6 Mb deletion including the whole SALL1 gene, and yet another sporadic case was found to carry an intragenic deletion of 3384 bp. In all affected persons, the TBS phenotype is rather mild as compared to the phenotype resulting from point mutations. These results confirm that SALL1 haploinsufficiency is sufficient to cause a mild TBS phenotype but suggest that it is not sufficient to cause the severe, classical form. It therefore seems that there is a different contribution of SALL1 gene function to mouse and human embryonic development.

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“…[1][2][3][4] In Drosophila, spalt is a homeotic gene that is essential for the development of posterior head and anterior tail segments. It plays an important role in terminal differentiation of photoreceptors, tracheal development, 5 and wing vein placement.…”

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confidence: 99%

Differential expression of the novel oncogene, SALL4, in lymphoma, plasma cell myeloma, and acute lymphoblastic leukemia

Cui

Kong

Ma³

et al. 2006

Modern Pathology

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CanadaSALL4, a newly identified zinc-finger transcriptional factor important for embryonic development, is mapped to chromosome 20q13. Previously, we reported that SALL4 was constitutively expressed in acute myeloid leukemia and SALL4 transgenic mice developed acute myeloid leukemia. In this study, we aimed to survey SALL4 protein expression in benign and neoplastic hematopoietic tissues in addition to acute myeloid leukemia using immunostaining with a polyclonal anti-SALL4 antibody. Primary hematological tumors (178) and 15 benign hematopoietic tissues were examined. Reverse transcription-polymerase chain reaction was also performed to detect SALL4 mRNA expression on eight precursor B-cell lymphoblastic leukemia/lymphomas, 10 benign hematopoietic tissues, and seven hematopoietic cancer cell lines. Of the benign tissues, SALL4 expression was detectable only in CD34 þ hematopoietic stem/progenitor cells (2/2 at protein level, 3/3 at RNA level). In neoplastic tissues, only precursor B-cell lymphoblastic leukemia/lymphomas had detectable SALL4 (12/16 at protein level, 7/8 at RNA level), similar to that observed in acute myeloid leukemia. Of the seven cell lines examined, only those derived from acute myeloid leukemia and precursor B-cell lymphoblastic leukemia/ lymphomas were positive. To conclude, SALL4 expression is normally restricted to CD34 þ hematopoietic stem/ progenitor cells. The persistence of SALL4 expression in leukemic blasts in precursor B-cell lymphoblastic leukemia/lymphomas resembles to what we observed in acute myeloid leukemia, and correlates with the maturation arrest of these cells. We have shown in our previous study that the constitutive expression of SALL4 in mice can lead to acute myeloid leukemia development. The similar expression pattern of SALL4 in acute myeloid leukemia and B-cell lymphoblastic leukemia/lymphomas suggests that these two disease entities may share similar biological features and/or mechanisms of leukemogenesis. More definite studies to investigate the role of SALL4 in the pathogenesis of B-cell lymphoblastic leukemia/lymphomas are needed in the future to address this question.

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Isolation, Characterization, and Organ-Specific Expression of Two Novel Human Zinc Finger Genes Related to theDrosophilaGenespalt

Cited by 138 publications

References 7 publications

ZNF797 plays an oncogenic role in gastric cancer

ZNF797 plays an oncogenic role in gastric cancer

Detection of heterozygousSALL1 deletions by quantitative real time PCR proves the contribution of aSALL1 dosage effect in the pathogenesis of Townes-Brocks syndrome

Differential expression of the novel oncogene, SALL4, in lymphoma, plasma cell myeloma, and acute lymphoblastic leukemia

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