Okihiro syndrome is caused by SALL4 mutations

Kohlhase, Jürgen; Heinrich, Marielle; Schubert, L; Liebers, Manuela; Kispert, Andreas; Laccone, Franco; Turnpenny, Peter D.; Winter, R M; Reardon, W

doi:10.1093/hmg/11.23.2979

Cited by 287 publications

(250 citation statements)

References 32 publications

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“…33,34 In humans, SALL4 is located on chromosome 20q13.13-13.2. 35 As in other species, SALL4 is essential to human development, and mutations in SALL4 lead to acro-renal-ocular and Okihiro syndromes. 33,35 In human embryonic stem cells, SALL4 is essential to maintain embryonal stem cell pluripotency and self-renewal by forming a regulatory network with OCT4, NANOG, and SOX2.…”

Section: Discussionmentioning

confidence: 99%

“…35 As in other species, SALL4 is essential to human development, and mutations in SALL4 lead to acro-renal-ocular and Okihiro syndromes. 33,35 In human embryonic stem cells, SALL4 is essential to maintain embryonal stem cell pluripotency and self-renewal by forming a regulatory network with OCT4, NANOG, and SOX2. 26,[28][29][30]36,37 In this study, SALL4 was found to be strongly positive in >90% of tumor cells in all metastatic seminomas, dysgerminomas, embryonal carcinomas, and 14 of 15 yolk sac tumors.…”

Section: Discussionmentioning

confidence: 99%

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SALL4 is a novel sensitive and specific marker for metastatic germ cell tumors, with particular utility in detection of metastatic yolk sac tumors

Cao¹,

Humphrey²,

Allan³

2009

Cancer

143

115

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BACKGROUND:The correct diagnosis of metastatic germ cell tumors is critical, because these tumors can be effectively treated and are even cured with modern therapy. Their histopathologic diagnosis can be challenging without immunohistochemical markers, which currently have limitations. SALL4 is a novel stem cell marker essential to maintain pluripotency and self‐renewal of embryonic stem cells. In the current study, the authors investigated the utility of SALL4 as a potential diagnostic marker for metastatic germ cell tumors.METHODS:Ninety metastatic germ cell tumors from testis, ovary, and extragonadal sites were stained with a monoclonal SALL4 antibody. In addition, 170 metastatic nongerm cell malignancies, including 158 carcinomas (6 head and neck, 8 thyroid, 12 lung, 8 breast, 7 hepatocellular, 3 cholangiocarcinomas, 2 ampullary, 10 pancreatic, 18 gastric, 15 esophageal, 10 renal cell, 10 urothelial, 12 prostatic, 18 ovarian, 6 uterine, and 13 colonic) and 12 melanomas, were also stained to test SALL4 specificity.RESULTS:All 22 seminomas, 7 dysgerminomas, 22 embryonal carcinomas, and 14 of 15 yolk sac tumors displayed strong and diffuse SALL positivity in >90% of tumor cells (80% of tumor cells were strongly positive in the remaining yolk sac tumor). Five of 7 choriocarcinomas and 9 of 18 teratomas were also variably positive for SALL4. In contrast, only 10 (esophageal, gastric, and colonic adenocarcinomas) of 170 metastatic somatic tumors demonstrated focally weak SALL4 reactivity (<25% tumor cells).CONCLUSIONS:SALL4 is a novel sensitive and highly specific marker for metastatic germ cell tumors, and is particularly useful for detecting metastatic yolk sac tumors. Cancer 2009. © 2009 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

SALL4 is a novel sensitive and specific marker for metastatic germ cell tumors, with particular utility in detection of metastatic yolk sac tumors

Cao¹,

Humphrey²,

Allan³

2009

Cancer

143

115

View full text Add to dashboard Cite

show abstract

“…[20][21][22][23] SALL4 forms a regulatory circuit with OCT4, NANOG, and SOX2 to maintain embryonic stem cell pluripotency and self-renewal. [24][25][26][27][28][29] In this self-stabilizing network, SALL4 regulates OCT4 transcription, suggesting acting upstream of OCT4.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic utility of SALL4 in primary germ cell tumors of the central nervous system: a study of 77 cases

et al. 2009

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Primary germ cell tumors of the central nervous system (CNS) sometimes pose diagnostic difficulty. In this study we analyzed the diagnostic utility of a novel marker, SALL4, in 77 such tumors (59 pure and 18 mixed) consisting of the following tumors/tumor components: 49 germinomas, 7 embryonal carcinomas, 27 yolk sac tumors, 3 choriocarcinomas, and 14 teratomas. We also stained SALL4 in 99 primary non-germ cell tumors to test SALL4 specificity. We compared SALL4 with OCT4 in all germ cell tumors and compared SALL4 with a-fetoprotein and glypican-3 in all yolk sac tumors. The staining was semiquantitatively scored as 0 (no staining), 1 þ (o ¼ 30%), 2 þ (31-60%), 3 þ (61-90%), and 4 þ (490%). Strong SALL4 staining was observed in all 49 germinomas (4 þ in 48, 3 þ in 1), 7 embryonal carcinomas (all 4 þ ), and 27 yolk sac tumors (1 þ in 1, 2 þ in 2, 3 þ in 7, 4 þ in 17). SALL4 staining, 1 þ weak to focally strong, was observed in 2 of 3 choriocarcinomas (in mononucleated trophoblasts) and in 9 of 14 teratomas (in primitive neuroepithelium and teratomatous glands). All germinomas and embryonal carcinomas showed strong OCT4 staining (4 þ in all except 1 germinoma with 3 þ ), whereas other germ cell tumors were negative. Out of 27 yolk sac tumors, 26 showed positive a-fetoprotein staining (1 þ in 9, 2 þ in 7, 3 þ in 5, and 4 þ in 5). All yolk sac tumors showed positive glypican-3 staining (1 þ in 6, 2 þ in 6, 3 þ in 7, and 4 þ in 8). The mean percentage of yolk sac tumor cells stained was 84% with SALL4, 45% with a-fetoprotein, and 63% with glypican-3 (Po0.01). No non-germ cell tumors showed SALL4 staining. Our results indicate that SALL4 is a novel sensitive diagnostic marker for primary germ cell tumors of the CNS with high specificity. SALL4 is a more sensitive marker than a-fetoprotein and glypican-3 for yolk sac tumors.

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“…with reported mutations associated with cardiac septal defects in the human population (Al-Baradie et al, 2002;Kohlhase et al, 2002;Ching et al, 2005;Koshiba-Takeuchi et al, 2006). However, it is unclear whether Tbx5 can directly regulate the expression of these genes in the developing heart in vivo.…”

Section: Discussionmentioning

confidence: 99%

Microarray analysis of Tbx5‐induced genes expressed in the developing heart

Plageman

Yutzey

2006

Developmental Dynamics

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Tbx5 is a member of the T-box family of transcription factors and is associated with Holt-Oram syndrome (HOS), a congenital disorder characterized by heart and limb defects. Although implicated in several processes during development, only a few genes regulated by Tbx5 have been reported. To identify candidate genes regulated by Tbx5 during heart development, a microarray approach was used. A cardiacderived mouse cell line (1H) was infected with adenoviruses expressing Tbx5 or ␤-galactosidase and RNA was isolated for analysis using an Affymetrix gene chip representing over 39,000 transcripts. Real-time reverse transcriptase-polymerase chain reaction confirmed Tbx5 induction of a subset of the genes, including nppa, photoreceptor cadherin, brain creatine kinase, hairy/enhancer-of-split related 2, and gelsolin. In situ hybridization analysis indicated overlapping expression of these genes with tbx5 in the embryonic mouse heart. In addition, the effect of HOS-associated mutations on the ability of Tbx5 to induce target gene expression was evaluated. Together, these data identify several genes induced by Tbx5 that are potentially important during cardiac development. These genes represent new candidate gene targets of Tbx5 that may be related to congenital heart malformations associated with HOS. Developmental Dynamics 235:2868 -2880, 2006.

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Okihiro syndrome is caused by SALL4 mutations

Cited by 287 publications

References 32 publications

SALL4 is a novel sensitive and specific marker for metastatic germ cell tumors, with particular utility in detection of metastatic yolk sac tumors

SALL4 is a novel sensitive and specific marker for metastatic germ cell tumors, with particular utility in detection of metastatic yolk sac tumors

Diagnostic utility of SALL4 in primary germ cell tumors of the central nervous system: a study of 77 cases

Microarray analysis of Tbx5‐induced genes expressed in the developing heart

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