Aberrant Overexpression of Satellite Repeats in Pancreatic and Other Epithelial Cancers - CTC Technology - Massachusetts General Hospital, Boston, MA

Published Online 13 January 2011
< Science Express Index Science DOI: 10.1126/science.1200801 •Report
Aberrant Overexpression of Satellite Repeats in Pancreatic and Other Epithelial Cancers

David T. Ting1,*, Doron Lipson2,*, Suchismita Paul1, Brian W. Brannigan1 , Sara Akhavanfard1, Erik J. Coffman1, Gianmarco Contino1, Vikram Deshpande1, A. John Iafrate1, Stan Letovsky2, Miguel N. Rivera1, Nabeel Bardeesy1, Shyamala Maheswaran1 and Daniel A. Haber1,3,†
+ Author Affiliations

1Massachusetts General Hospital Cancer Center and Departments of Medicine, Pathology and Surgery, Harvard Medical School, Boston, MA 02114, USA.
2Helicos BioSciences Corporation, One Kendall Square, Cambridge, MA 02139, USA.
3Howard Hughes Medical Institute.
†To whom correspondence should be addressed. E-mail: haber@helix.mgh.harvard.edu
↵* These authors contributed equally to this work.

Abstract
Satellite repeats in heterochromatin are transcribed into noncoding RNAs that have been linked to gene silencing and maintenance of chromosomal integrity. Using digital gene expression analysis, we show that these transcripts are greatly overexpressed in mouse and human epithelial cancers. In 8 of 10 mouse pancreatic ductal adenocarcinomas (PDAC), pericentromeric satellites accounted for a mean 12% (range 1 to 50%) of all cellular transcripts, a mean 40-fold increase over normal tissue. In 15/15 human PDACs, alpha satellite transcripts were most abundant and HSATII transcripts were highly specific for cancer. Similar patterns were observed in cancers of lung, kidney, ovary, colon, and prostate. Derepression of satellite transcripts correlated with overexpression of the LINE-1 retrotransposon and with aberrant expression of neuroendocrine-associated genes proximal to LINE-1 insertions. The overexpression of satellite transcripts in cancer may reflect global alterations in heterochromatin silencing and could potentially be useful as a biomarker for cancer detection.

Received for publication 28 September 2010.
Accepted for publication 4 January 2011.




ONCOLOGÍA
Actualidad Ultimas noticias - JANOes y agencias
Identifican nuevas regiones genéticas activas en el cáncer
JANO.es y agencias · 14 Enero 2011 09:52

El hallazgo supone un paso importante para un mejor diagnóstico y conocimiento de la enfermedad.

Investigadores del Centro Oncológico del Hospital General de Massachusetts, Estados Unidos, han descubierto que determinadas secuencias de ADN, conocidas como ‘repeticiones por satélite’, experimentan una sobreexpresión masiva cuando aparecen tumores. La investigación de este fenómeno supone un paso importante en el mejor diagnóstico y conocimiento del cáncer.

“Las repeticiones por satélite conforman una gran parte de nuestro genoma, pero se pensaba que eran inactivas”, explica David Ting, investigador del Centro Oncológico de Massachusetts y coautor del artículo. Sin embargo, esta investigación, desarrollada con nuevas técnicas de secuenciación, muestra que estas regiones son muy activas en el cáncer.

Los investigadores han descubierto que esta sobreexpresión de las repeticiones por satélite comienza pronto en el desarrollo del tumor, por lo que resulta fundamental para lograr una detección temprana en el paciente. Para llevar a cabo el estudio, los investigadores han utilizado un sistema digital de análisis de expresión de genes denominado “secuenciación de una sola molécula de próxima generación”.

Posible biomarcador del cáncer

Gracias a este sistema pudieron comprobar, en un cáncer pancreático de ratón, que el ADN satélite se expresaba en niveles que superaban 100 veces los valores que registraba en tejidos normales. Por otro lado, al analizar muestras de cáncer epitelial (el tipo más común de tumor) se comprobó que tanto en tumores de colon como de pulmón, de ratón se repetían los mismos niveles.

“Nuestra esperanza es que esta anomalía (hasta ahora desconocida) sirva como marcador biológico en el diagnóstico del cáncer y arroje luz sobre los mecanismos mediante los cuales se desarrolla el tumor”, añade Daniel Haber, director del centro oncológico y autor principal.

El estudio en células cancerígenas humanas obtuvo resultados similares en la mayoría de los cánceres estudiados, que incluyen los tumores de páncreas, pulmón y próstata. Si se confirmara en los ensayos clínicos prospectivos, “la expresión del ARN satélite puede proporcionar un biomarcador nuevo y altamente específico relacionado con varios tipos de cánceres epiteliales”, concluye Ting.


Science (2011); doi: 10.1126/science.1200801
Aberrant Overexpression of Satellite Repeats in Pancreatic and Other Epithelial Cancers | Science/AAAS

Centro Oncológico Hospital General de Massachusetts
Massachusetts General Hospital: Cancer Center Home Page - Massachusetts General Hospital, Boston, MA.

Actualidad Ultimas noticias - JANOes y agencias - Identifican nuevas regiones geneticas activas en el cancer - JANO.es - ELSEVIER




Circulating Tumor Cell (CTC) Blood Test: FAQs
How does the CTC technology work?
The CTC blood test uses a tiny microchip-based device that detects and analyzes tumor cells in the bloodstream. In clinical trials, researchers have been able to detect tumor cells in small samples of patients’ blood, helping to determine whether or not cancer fighting therapies are working. This technology has great promise as a cancer monitoring test, helping physicians see the effectiveness of therapies and checking for recurrence. It could also potentially be used for detection; however further testing is still needed.

Can I be tested for cancer using CTC technology?
The CTC blood test is not yet available to patients as a cancer screening tool. Recent news stories have highlighted our new partnership with Johnson & Johnson, which will help our researchers develop and perfect the technology at a faster pace. Our collaboration is just beginning, but we are hopeful that it could lead to the test being made available to patients in the future.

When will the CTC test be available?
The CTC blood test has shown great promise in clinical trials. Our physicians and researchers are working closely with scientists at Veridex, LLC – a Johnson & Johnson company – to accelerate the production, testing and availability of the CTC test. As with any cancer breakthrough, we want to bring this technology to all patients as soon as possible. However, since this technology is so new it could take years to be perfected to the point where it is widely available to cancer patients and eventually to the general public.

Can I enroll in a clinical trial of the CTC test?
Clinical research on circulating tumor cells is still in its early stages. The CTC technology being developed is experimental, and currently no clinical decisions can be made based on CTC analyses. The next generation of clinical trials is being designed. When these become available, the Mass General Cancer Center will post this information on its website. Clinical trial participants must be a cancer patient at Mass General and identified as an appropriate candidate by their oncologist.

If you have cancer and wish to be seen at Mass General please call: 877-726-5130
CTC Technology - Massachusetts General Hospital, Boston, MA
CTC Technology - Massachusetts General Hospital, Boston, MA