cTAGE: A Cutaneous T Cell Lymphoma Associated Antigen Family with Tumor-Specific Splicing

Usener, Dirk; Schadendorf, Dirk; Koch, Joachim; Dübel, Stefan; Eichmüller, Stefan B.

doi:10.1046/j.1523-1747.2003.12318.x

Cited by 52 publications

(16 citation statements)

References 40 publications

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“…A number of critical seminal studies using serological detection of CTCL antigens suggested that a number of Cancer Testis (CT) genes might be heterogeneously expressed in CTCL patients(16–18, 39). Furthermore, additional testing by RT-PCR and Northern Blot confirmed the expression of some CT antigens in a subset of CTCL lesional skin(18, 19).…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies suggested based on serology and limited PCR in 20 patients that cTAGE1 (Cutaneous T-Cell Lymphoma-Associated Antigen 1) is expressed only in 30% of CTCL patients(17, 39). However, in our study we found this gene to be robustly expressed in a majority of CTCL patients and patient-derived cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…However, in our study we found this gene to be robustly expressed in a majority of CTCL patients and patient-derived cell lines. One possibility that might explain this discrepancy is the presence of various splicing variants for this gene(39). Hence, use of different primers targeting different portions of the gene may produce discrepancies.…”

Section: Discussionmentioning

confidence: 99%

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Ectopic Expression of Cancer–Testis Antigens in Cutaneous T-cell Lymphoma Patients

Litvinov

Cordeiro

Huang

et al. 2014

Clinical Cancer Research

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Purpose The pathogenesis of CTCL remains only partially understood. A number of recent studies attempted to identify novel diagnostic markers and future therapeutic targets. One group of antigens, cancer-testis (CT) antigens, normally present solely in testicular germ cells, can be ectopically expressed in a variety of cancers. Currently only a few studies attempted to investigate the expression of CT antigens in CTCL. Experimental Design In the present work we test the expression of CT genes in a cohort of CTCL patients, normal skin samples, skin from benign inflammatory dermatoses and in patient-derived CTCL cells. We correlate such expression with the p53 status and explore molecular mechanisms behind their ectopic expression in these cells. Results Our findings demonstrate that SYCP1, SYCP3, REC8, SPO11 and GTSF1 genes are heterogeneously expressed in CTCL patients and patient-derived cell lines, while cTAGE1 was found to be robustly expressed in both. Mutated p53 status did not appear to be a requirement for the ectopic expression of CT antigens. While T cell stimulation resulted in a significant upregulation of STAT3 and JUNB expression, it did not significantly alter the expression of CT antigens. Treatment of CTCL cells in-vitro with Vorinostat or Romidepsin Histone Deacetylase inhibitors resulted in a significant dose-dependent upregulation of mRNA, but not protein. Further expression analysis demonstrated that SYCP1, cTAGE1 and GTSF1 were expressed in CTCL, but not in normal skin or benign inflammatory dermatoses. Conclusions A number of CT genes are ectopically expressed in CTCL patients and can be used as biomarkers or novel targets for immunotherapy.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Ectopic Expression of Cancer–Testis Antigens in Cutaneous T-cell Lymphoma Patients

Litvinov

Cordeiro

Huang

et al. 2014

Clinical Cancer Research

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“…Three additional novel gene fusions were also discovered and validated in a cohort of 54 tumor cases, CTAGE5-KHDRBS3, SDK1-AMACR , and RAD50-PDLIM4 [14]. CTAGE5 (cutaneous T-cell lymphoma–associated antigen 5), previously shown to be overexpressed in many cancer cell lines [36], was shown to fuse with KHDRBS3 (KH domain containing, RNA binding, signal transduction associated 3), a gene also associated with cancer [37], at a frequency of 37% [14]. SDK1 (located within a common fragile site of chromosome 7p) [38] was also found fused to AMACR (an androgen responsive gene) [39] at a frequency of 24%.…”

Section: Gene Fusion Stratification Of Prostate Cancersmentioning

confidence: 99%

Recurrent Rearrangements in Prostate Cancer: Causes and Therapeutic Potential

White

Feng²,

Maher³

2013

CDT

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DNA damage and genetic rearrangements are hallmarks of cancer. However, gene fusions as driver mutations in cancer have classically been a distinction in leukemia and other rare instances until recently with the discovery of gene fusion events occurring in 50 to 75% of prostate cancer patients. The discovery of the TMPRSS2-ERG fusion sparked an onslaught of discovery and innovation resulting in a delineation of prostate cancer via a molecular signature of gene fusion events. The increased commonality of high-throughput sequencing data coupled with improved bioinformatics approaches not only elucidated the molecular underpinnings of prostate cancer progression, but the mechanisms of gene fusion biogenesis. Interestingly, the androgen receptor (AR), already known to play a significant role in prostate cancer tumorigenesis, has recently been implicated in the processes resulting in gene fusions by inducing the spatial proximity of genes involved in rearrangements, promoting the formation of double-strand DNA breaks (DSB), and facilitating the recruitment of proteins for non-homologous end-joining (NHEJ). Our increased understanding of the mechanisms inducing genomic instability may lead to improved diagnostic and therapeutic strategies. To date, the majority of prostate cancer patients can be molecularly stratified based on their gene fusion status thereby increasing the potential for tailoring more specific and effective therapies.

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“…Todas estas alteraciones darían lugar a un potencial Ag específico de tumor. De hecho, se han detectado respuestas inmunológicas específicas contra algunos determinantes antigénicos derivados de proteínas con splicing anóma-lo en pacientes con cáncer [49][50][51][52][53][54][55][56][57][58] .…”

Section: Splicing Alternativounclassified

Vacuna idiotípica en el tratamiento del linfoma folicular: situación actual y perspectivas futuras

Zabalegui¹,

Cerio²,

Inogés³

et al. 2009

Anales Sis San Navarra

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RESUMENEl linfoma folicular (LF) está considerado como el segundo tipo de linfoma no-Hodgkin más común, representando más del 20% del total de los linfomas. Es una enfermedad de progresión lenta y curso indolente en la que, a pesar de la buena respuesta al tratamiento, las recaídas son muy frecuentes y cada vez es más difí-cil conseguir respuestas completas. Por ello, se puede considerar que hasta el momento, el LF es incurable. La búsqueda continua de nuevas estrategias terapéu-ticas en enfermedades neoplásicas, junto con un mejor conocimiento del sistema inmunitario, ha llevado a la aparición de una nueva disciplina, conocida con el nombre de inmunoterapia, que aprovecha la capacidad del sistema inmunitario de atacar lo extraño sin dañar lo propio. El LF es un tumor muy apropiado para este tipo de tratamiento por presentar un antígeno específi-co de tumor: el idiotipo de la inmunoglobulina monoclonal expresada en la membrana de todas las células tumorales. Se han realizado diversos estudios en los que se ha probado la inmunoterapia como tratamiento complementario al tratamiento convencional. Recientemente, nuestro grupo ha publicado un estudio en el que se observa claramente que los resultados que se obtienen tras la vacunación idiotípica, cuando se consigue la inmunización adecuada del paciente, son mejores que los obtenidos con quimioterapia sola. En este sentido, es necesario seguir investigando para aclarar si la vacunación idiotípica pudiera no sólo mantener remisiones completas duraderas en los pacientes vacunados, sino incluso conseguir la curación de los mismos. Por ello, resulta interesante abordar un mejor planteamiento de los ensayos clínicos, la mejora de la producción de la vacuna y el estudio de mecanismos de la célula tumoral capaces de modificar la inmunoglobulina específica del tumor.Palabras clave. Linfoma folicular. Inmunoterapia. Vacuna idiotípica. Glicosilación. Splicing alternativo. ABSTRACTFollicular lymphoma is the second most prevalent non-Hodgkin lymphoma, representing 20% of all lymphomas. Follicular lymphoma is an indolent disease with a slow progression in which, although exhibiting a good response to treatment, relapse is very frequent and complete remission is not easy to maintain. Therefore, the disease is regarded as incurable. The search for new therapeutic strategies, together with a better understanding of the immune system, has led to the emergence of a new treatment named immunotherapy. Follicular lymphoma is a malignancy suitable for this kind of treatment given the fact that it is characterized by presenting a unique tumour-specific antigen: the idiotype of the monoclonal immunoglobulin displayed on the membrane of tumour cells. Several studies have been conducted to test immunotherapy as complementary to conventional treatment. In a previous study by our group, a clear benefit was evident is obtained after idiotypic vaccination, when an adequate immunization of the patient is obtained, in comparison to chemotherapy alone. In this sense, analysis is needed of whether idi...

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cTAGE: A Cutaneous T Cell Lymphoma Associated Antigen Family with Tumor-Specific Splicing

Cited by 52 publications

References 40 publications

Ectopic Expression of Cancer–Testis Antigens in Cutaneous T-cell Lymphoma Patients

Ectopic Expression of Cancer–Testis Antigens in Cutaneous T-cell Lymphoma Patients

Recurrent Rearrangements in Prostate Cancer: Causes and Therapeutic Potential

Vacuna idiotípica en el tratamiento del linfoma folicular: situación actual y perspectivas futuras

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