SOX2 amplification is a common event in squamous cell carcinomas of different organ sites

Maier, Sebastian; Wilbertz, Theresia; Braun, Martin; Scheble, Veit; Reischl, Markus; Mikut, Ralf; Menon, Roopika; Nikolov, P; Petersen, Karl-Georg; Beschorner, Christine; Moch, Holger; Kakies, Christoph; Protzel, Chris; Bauer, Jürgen; Soltermann, Alex; Fend, Falko; Staebler, Annette; Lengerke, Claudia; Perner, Sven

doi:10.1016/j.humpath.2010.11.010

Cited by 100 publications

(95 citation statements)

References 32 publications

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“…9,15,25 Besides the lung, SOX2 has been found to be amplified and expressed in squamous cell carcinomas originating from other organ sites, predominantly derived from the embryonic foregut. 9,21,22 Recently, we found SOX2 to be amplified and expressed in squamous cell carcinomas originating from non-foregut tissues, such as the skin, the cervix, and the penis, 23 indicating that SOX2 might be a general marker for squamous cell carcinoma differentiation regardless the tissue of origin. Squamous carcinogenesis from diverse body sites may thus share similar underlying mechanisms.…”

Section: Sox2 In Squamous Cell Carcinomas From Other Organ Sitesmentioning

confidence: 97%

“…17,20 SOX2 may have similar oncogenic effects in other organs of foregut and non-foregut origin, since amplification and expression also occur in squamous cell carcinomas of the oral cavity, as well as in esophageal and gastric tumors. 9,[21][22][23] Recently, SOX2 expression has been detected in early-stage breast carcinoma. 24 These data suggest that expression of SOX2 drives oncogenesis and therefore overexpression in tumors may be associated with a more aggressive tumor phenotype and poorer clinical outcome.…”

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confidence: 99%

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SOX2 gene amplification and protein overexpression are associated with better outcome in squamous cell lung cancer

Wilbertz¹,

Wagner

Petersen³

et al. 2011

Modern Pathology

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The transcription factor SOX2 (3q26.3-q27) is a key regulator of foregut development and an embryonic stem cell factor cooperating during induction of pluripotency in terminally differentiated somatic cells. Recently, we found SOX2 to be amplified in a subset of squamous cell lung and esophageal cancers. The aim of this study was to explore the prognostic role of SOX2 in a large series of squamous cell carcinomas and adenocarcinomas of the lung. A total of 891 samples from two independent population-based cohorts were assessed by fluorescence in situ hybridization and immunohistochemistry. Furthermore, we assessed for associations between SOX2 amplification/upregulation and clinicopathological features. Similar results were found in the two cohorts. Within squamous cell carcinoma cases, 8% high-level as well as 68 and 65% low-level SOX2 amplifications occurred in the two cohorts, respectively. In adenocarcinomas, no high-level amplification was found and low-level amplification occurred in 6% of the two cohorts. Within squamous cell carcinomas of one cohort, SOX2 amplification was associated with lower tumor grade, while higher levels of SOX2 expression were related to younger age, smaller tumor size, and lower probability of angiolymphatic invasion and metastasis. High SOX2 expression levels proved to be a marker for prolonged overall survival among patients with squamous cell carcinomas. In conclusion, SOX2 amplification and upregulation are frequent events in squamous cell carcinomas of the lung and are associated with indicators of favorable prognosis. Modern Pathology (2011) 24, 944-953;

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Section: Sox2 In Squamous Cell Carcinomas From Other Organ Sitesmentioning

confidence: 97%

mentioning

confidence: 99%

SOX2 gene amplification and protein overexpression are associated with better outcome in squamous cell lung cancer

Wilbertz¹,

Wagner

Petersen³

et al. 2011

Modern Pathology

Self Cite

167

155

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“…Specific real-time PCR primers (Supporting Information Table S2) were designed for SOX2, SOX2OT, SOX2OT-S1, SOX2OT-S2, OCT4, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) (GenBank accession numbers: NM_003106.2, NR_004053.2, JN711430.1, JN882275.1, NM_002701.4, NM_002046.3, respectively), using AlleleID 6.0 software (Primer BioSoft, Palo Alto, CA; www.premierbiosoft.com) and Gene Runner software (version 3.02; Hastings Software, Inc.). TaKaRa SYBR Premix Ex TaqII master mix (23), supplemented with ROX reference Dye II, were used for all real-time PCR reactions. For compensating variations in the amount of input RNA and the efficacy of reverse transcriptase, GAPDH mRNA was also quantified as an internal control, and the expression of other genes was normalized to its expression value.…”

Section: Rt-pcr and Quantitative Real-time Pcrmentioning

confidence: 99%

Two Novel Splice Variants of SOX2OT, SOX2OT-S1, and SOX2OT-S2 are Coupregulated with SOX2 and OCT4 in Esophageal Squamous Cell Carcinoma

et al. 2014

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Long noncoding RNAs (lncRNAs) have emerged as new regulators of stem cell pluripotency and tumorigenesis. The SOX2 gene, a master regulator of pluripotency, is embedded within the third intron of a lncRNA known as SOX2 overlapping transcript (SOX2OT). SOX2OT has been suspected to participate in regulation of SOX2 expression and/or other related processes; nevertheless, its potential involvement in tumor initiation and/or progression is unclear. Here, we have evaluated a possible correlation between expression patterns of SOX2OT and those of master regulators of pluripotency, SOX2 and OCT4, in esophageal squamous cell carcinoma (ESCC) tissue samples. We have also examined its potential function in the human embryonic carcinoma stem cell line, NTERA2 (NT2), which highly expresses SOX2OT, SOX2, and OCT4. Our data revealed a significant coupregulation of SOX2OT along with SOX2 and OCT4 in tumor samples, compared to the non-tumor tissues obtained from the margin of same tumors. We also identified two novel splice variants of SOX2OT (SOX2OT-S1 and SOX2OT-S2) which coupregulated with SOX2 and OCT4 in ESCCs. Suppressing SOX2OT variants caused a profound alteration in cell cycle distribution, including a 5.9 and 6.9 time increase in sub-G1 phase of cell cycle for SOX2OT-S1 and SOX2OT-S2, respectively. The expression of all variants was significantly diminished, upon the induction of neural differentiation in NT2 cells, suggesting their potential functional links to the undifferentiated state of the cells. Our data suggest a part for SOX2OT spliced variants in tumor initiation and/or progression as well as regulating pluripotent state of stem cells. STEM CELLS 2014;32:126-134

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“…SOX2 amplification was identified by FISH in 20-23% of lung cancer; 11-15% of oesophagus cancer, 5-28 % of cervix SCC and 28% of skin cancer. 4,5,12 In lung cancer, SOX2 overexpression is associated with favourable prognosis, whereas the relevance of SOX2 expression for prognosis of HNSCC is controversial. [13][14][15] Sentinel node biopsy (SNB) of the N0 neck in early oral SCC has been shown in several studies to reliably detect occult neck metastasis with negative predictive values >95%.…”

Section: Introductionmentioning

confidence: 99%

High sex determining region Y-box 2 expression is a negative predictor of occult lymph node metastasis in early squamous cell carcinomas of the oral cavity

Züllig

Roessle

Weber

et al. 2013

European Journal of Cancer

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SOX2 amplification is a common event in squamous cell carcinomas of different organ sites

Cited by 100 publications

References 32 publications

SOX2 gene amplification and protein overexpression are associated with better outcome in squamous cell lung cancer

SOX2 gene amplification and protein overexpression are associated with better outcome in squamous cell lung cancer

Two Novel Splice Variants of SOX2OT, SOX2OT-S1, and SOX2OT-S2 are Coupregulated with SOX2 and OCT4 in Esophageal Squamous Cell Carcinoma

High sex determining region Y-box 2 expression is a negative predictor of occult lymph node metastasis in early squamous cell carcinomas of the oral cavity

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