lundi 31 octobre 2011

Mutated genes in cancer (27) – GATA1


In databases:

● Entrez ( 2623 or GATA1
● Ensembl ( ENSG00000102145
● UniProt ( P15976
● GeneCards ( GATA1
● HGNC ( 4170 or GATA1

Gene locus:


Protein name:

GATA binding protein 1 (globin transcription factor 1)

Protein Size:

413 amino acids; about 43 kDa


The gene encodes a protein which belongs to the GATA family of transcription factors. GATA1 is essential for erythroid and megakaryocytic development. It helps transcribe the α-spectrin structural protein which is critical for the shape of red blood cells.

Cancer-related alterations:

Somatic mutations are seen in hematopoietic and lymphoid tissue tumors. They alter the first 80 amino acids of the protein.

Acquired somatic mutations in GATA1 occur in virtually all children with Down Syndrome (DS) and congenital transient myeloproliferative syndrome (TMD) or acute megakaryocytic leukemia (AMKL). The mutations have also been detected in umbilical cord blood of DS patients and in fetal liver of aborted DS embryos. The mutations occur in-utero probably during fetal liver hematopoiesis. They consist of insertions, deletions and base substitution in exon 2 and vicinity and all result in elimination of the full length GATA1 protein with preservation of the GATA1s isoform.

References (open access):

GATA Transcription Factors and Cancer. Zheng R, Blobel GA. Genes Cancer. 2010 Dec;1(12):1178-88.

GATA-1 directly regulates p21 gene expression during erythroid differentiation. Papetti M, Wontakal SN, Stopka T, Skoultchi AI. Cell Cycle. 2010 May 15;9(10):1972-80.

Mutational spectrum at GATA1 provides insights into mutagenesis and leukemogenesis in Down syndrome. Cabelof DC, Patel HV, Chen Q, van Remmen H, Matherly LH, Ge Y, Taub JW. Blood. 2009 Sep 24;114(13):2753-63.

dimanche 30 octobre 2011

Anticancer molecules (63) – Molécules anticancéreuses (63)


Name : leuprolide acetate
Commercial names : Eligard, Lupron, Lupron Depot, Lupron Depot-Ped,  Lupron Depot-3 Month, Lupron Depot-4 Month, Viadur
Pharmacological class: GnRH analogue
Therapeutic class: antineoplastic
Action: Leuprolide acetate, an LH-RH agonist, acts as a potent inhibitor of gonadotropin secretion when given continuously in therapeutic doses. Animal and human studies indicate that after an initial stimulation, chronic administration of leuprolide acetate results in suppression of ovarian and testicular steroidogenesis. In males, testosterone is reduced to below castrate threshold. These decreases occur within two to four weeks after initiation of treatment. Long-term studies have shown that continuation of therapy with leuprolide acetate maintains testosterone below the castrate level for up to seven years

In 2011, leuprolide acetate is approved for palliative treatment of advanced prostate cancer.


Nom: acétate de leuprolide
Noms commerciaux: Eligard, Lupron, Lupron Depot, Lupron Depot-Ped,  Lupron Depot-3 Month, Lupron Depot-4 Month, Viadur
Classe pharmacologique: analogue de la GnRH
Classe thérapeutique: antinéoplasiques
Action: l'acétate de leuprolide, un agoniste de la LH-RH, agit comme un puissant inhibiteur de la sécrétion de gonadotrophine lorsqu'il est administré en continu à des doses thérapeutiques. Des études animales et humaines montrent que, après une stimulation initiale, l'administration chronique de leuprolide acétate entraîne la suppression de la stéroïdogenèse ovarienne et testiculaire. Chez les mâles, la testostérone est réduite au-dessous du seuil de castration. Ces baisses se produisent au sein de deux à quatre semaines après l'initiation du traitement. Des études à long terme ont montré que la poursuite du traitement avec l'acétate de leuprolide maintient la testostérone en dessous du niveau de castration pour une période maximale de sept ans.

En 2011, l'acétate de leuprolide est approuvé pour le traitement palliatif du cancer avancé de la prostate.

samedi 29 octobre 2011

Press review (October 29, 2011) – Revue de presse (29 octobre 2011)

Male Breast Cancer: Limited Awareness Costs Lives, New Study Says‎
Men have a breast cancer incidence rate less than 1 percent of that of females, but when they do get the disease, it is often more advanced, according to a sweeping new study. The research, published earlier this month in the Journal of Clinical Oncology, looked at breast cancer in 6 countries over the last 40 years. Researchers found that men had poorer five-year survival rates than women, and the disease generally occurred later in life for them.
By Catherine Pearson. In Huffington Post

Lung cancer screening with X-rays isn't beneficial
Routine chest X-rays do not prevent lung cancer deaths, not even in smokers or former smokers, according to a big government study challenging a once common type of screening.
In USA Today

Doctors split on Avastin for breast cancer - survey
An international survey of cancer doctors shows that many question U.S. health advisers' 2010 rejection of Roche Holding's drug Avastin to treat advanced breast cancer.
By Andrew M. Seaman. Reuters

Double Trouble From HPV
Two new studies have come out that highlight significant news around HPV – Human Papillomavirus. HPV is known to increase the risk of cervical cancer in women significantly. Now, a study in the New England Journal of Medicine shows that an HPV vaccine that helps prevent HPV in women, can help prevent most anal cancers in gay men..
By Doc Gurley. In San Francisco Chronicle (blog)

Increase in Borderline Ovarian Cancer After IVF
Ovarian stimulation by in vitro fertilization (IVF) increases the risk for borderline ovarian tumors, but the risk for invasive ovarian cancer is not significantly increased, a new study concludes. It also found no increase in cancer risk with an increased number of IVF cycles. The study was published online October 26 in Human Reproduction.
By Becky McCall. In Medscape

Research makes it possible to predict how cancers will respond to chemo. Finding rewrites old theory of why chemo works
Challenging a half-century-old theory about why chemotherapy agents target cancer, scientists at Dana-Farber Cancer Institute have devised a test that can predict how effective the drugs will be by determining whether a patient's tumor cells are already "primed" for death. In a study published online by the journal Science on Oct. 27, the researchers report that cancer cells that are on the verge of self-destruction are more likely to succumb to certain chemotherapy agents than cancer cells that have yet to reach that stage. The discovery suggests that it may be possible to predict which cancer patients are most likely to benefit from chemotherapy, as well as to make chemotherapy drugs more effective by pushing tumor cells closer to the point of suicide.
In EurekAlert

Mummy Had History's Second-Oldest Prostate Cancer Case‎‎
Some 2,250 years ago in Egypt, a man known today only as M1 struggled with a long, painful, progressive illness. A dull pain throbbed in his lower back, then spread to other parts of his body, making most movements a misery. When M1 finally succumbed to the mysterious ailment between the ages of 51 and 60, his family paid for him to be mummified so that he could be reborn and relish the pleasures of the afterworld. Now an international research team has diagnosed what ailed M1: the oldest known case of prostate cancer in ancient Egypt and the second oldest case in the world
By Heather Pringle. In Wired News

NHS breast cancer screening to be reviewed
England’s breast cancer screening programme could be scaled back amid concerns from scientists that it is leading to women undergoing surgery unnecessarily.
By Martin Beckford. In

Cancer, the growing silent killer among the Ugandan population‎
Having dedicated October as a month to focus on cancer, we have been running stories on various types of the disease focusing on the causes, treatment, statistics and methods of prevention. As we wrap up our series, we look at the state of cancer in the country. Over the years, cancer has become more common with one in 500 people suffering from one type or another, a warning that if you have not yet checked or had screening for those types that can be screened, you should.
By Flavia Lanyero. In Daily Monitor

Les bienfaits du café contre le cancer de la peau se confirment
La consommation régulière de café réduirait les risques de cancer de la peau, montre une étude américaine.

Cancer du poumon: une radiographie annuelle ne réduit pas la mortalité
Des radiographies annuelles de la cage thoracique ne réduisent pas la mortalité résultant du cancer du poumon, selon une vaste étude clinique présentée mercredi aux Etats-Unis qui montre l'inutilité de cette procédure.

Ouverture du premier procès de l'amiante en Belgique‎
Le premier procès de victimes belges de l'amiante s'est ouvert lundi à Bruxelles, où le groupe belgo-suisse Eternit est accusé par une famille décimée par le cancer d'avoir négligé la nocivité de cette substance utilisée pendant des décennies dans la construction.

Le vaccin anti-papillomavirus humains préviendrait le cancer anal
Le vaccin contre les papillomavirus humains (HPV), transmis sexuellement et responsables de nombreux cancers utérins, s'est avéré efficace pour prévenir des infections et lésions anales pré-cancéreuses chez des hommes homosexuels, selon une étude clinique publiée mercredi.

Les cabines de bronzage favorisent les cancers‎
Ça chauffe pour les cabines de bronzage. Lors du 10e congrès international de l'Association américaine de recherche contre le cancer (AACR) qui vient de s'achever à Boston (États-Unis), les chercheurs ont une nouvelle fois pointé du doigt les méfaits des cabines à UV (rayons ultraviolets responsables du bronzage), les accusant de favoriser la survenue de cancers de la peau : le baso-cellulaire (le plus fréquent), le spino-cellulaire et le mélanome malin.
Par Anne Jouan. Dans Le Figaro

vendredi 28 octobre 2011

Focus : construct and Compare Gene Coexpression Networks with DAPfinder and DAPview

Background: DAPfinder and DAPview are novel BRB-ArrayTools plug-ins to construct gene coexpression networks and identify significant differences in pairwise gene-gene coexpression between two phenotypes.
Results: Each significant difference in gene-gene association represents a Differentially Associated Pair (DAP). Our tools include several choices of filtering methods, gene-gene association metrics, statistical testing methods and multiple comparison adjustments. Network results are easily displayed in Cytoscape. Analyses of glioma experiments and microarray simulations demonstrate the utility of these tools.
Conclusions: DAPfinder is a new user-friendly tool for reconstruction and comparison of biological networks.

Source: Construct and Compare Gene Coexpression Networks with DAPfinder and DAPview. Skinner Jeff, Kotliarov Yuri, Varma Sudhir, Mine Karina L, Yambartsev Anatoly, Simon Richard, Huyen Yentram (, Morgun Andrey ( BMC Bioinformatics. 2011 Jul 14;12(1):286.

Contexte: DAPfinder et DAPview sont de nouveaux « plug-ins » pour construire des réseaux de co-expression de gènes et pour identifier des différences significatives dans la co-expression de paires gène-gène entre deux phénotypes.
Résultats: chaque différence significative d’association gène-gène représente une paire différentiellement associée (DAP). Nos outils comprennent plusieurs choix de méthodes de filtrage, des métriques d’association gène-gène, des méthodes de test statistique et des ajustements statistiques de comparaison multiple. Les résultats obtenus sont facilement affiché dans « Cytoscape ». Les analyses des expériences sur gliome et des simulations sur biopuces démontrent l'utilité de ces outils.
Conclusions: DAPfinder est un nouvel outil convivial pour la reconstruction et la comparaison de réseaux biologiques.

Article (en anglais) librement accessible à l’adresse :

mercredi 26 octobre 2011

Mutated genes in cancer (26) – ASXL1


In databases :

● Entrez ( 171023 or ASLX1
● Ensembl ( ENSG00000171456
● UniProt ( Q8IXJ9
● GeneCards (  ASXL1
● HGNC ( 18318 or ASXL1

Gene locus:


Protein name:

Additional sex combs like 1

Protein Size:

1541 amino acids; about 165 kDa


ASXL1 is similar to the Drosophila additional sex combs gene, which encodes a chromatin-binding protein required for normal determination of segment identity in the developing embryo. The protein is a member of the Polycomb group of proteins, which are necessary for the maintenance of stable repression of homeotic and other loci. The protein is thought to disrupt chromatin in localized areas, enhancing transcription of certain genes while repressing the transcription of other genes. ASXL1 functions as either a coactivator or corepressor for the retinoid receptors retinoic acid receptor (RAR) and retinoid X receptor in a cell type-specific manner. These results support predictions of dual activator/repressor functions for mammalian ASXL proteins depending on cellular context.

Cancer-related alterations:

ASXL1 somatic mutations (insertions, deletions, substitutions) seem to be restricted to hematopoietic and lymphoid tissue tumors. Mutations have been observed in myelodysplastic syndromes (MDS), juvenile myelomonocytic leukemia (JMML), CMML (a disease classified as MDS/Myeloproliferative disorder), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), B-acute lymphoblastic leukemia (B-ALL) samples.
The most common mutation is an insertion at amino acid 646

References (open access):

Combined mutations of ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, RUNX1, TET2 and WT1 genes in myelodysplastic syndromes and acute myeloid leukemias. Rocquain J, Carbuccia N, Trouplin V, Raynaud S, Murati A, Nezri M, Tadrist Z, Olschwang S, Vey N, Birnbaum D, Gelsi-Boyer V, Mozziconacci MJ. BMC Cancer. 2010 Aug 2;10:401.

Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1. Tefferi A. Leukemia. 2010 Jun;24(6):1128-38.

Genetic analysis of transforming events that convert chronic myeloproliferative neoplasms to leukemias. Abdel-Wahab O, Manshouri T, Patel J, Harris K, Yao J, Hedvat C, Heguy A, Bueso-Ramos C, Kantarjian H, Levine RL, Verstovsek S. Cancer Res. 2010 Jan 15;70(2):447-52.

Focus: meta-analysis of multiple microarray datasets reveals a common gene signature of metastasis in solid tumors.

Metastasis is the number one cause of cancer deaths. Expression microarrays have been widely used to study metastasis in various types of cancer. We hypothesize that a meta-analysis of publicly available gene expression datasets in various tumor types can identify a signature of metastasis that is common to multiple tumor types. This common signature of metastasis may help us to understand the shared steps in the metastatic process and identify useful biomarkers that could predict metastatic risk.

We identified 18 publicly available gene expression datasets in the Oncomine database comparing distant metastases to primary tumors in various solid tumors which met our eligibility criteria. We performed a meta-analysis using a modified permutation counting method in order to obtain a common gene signature of metastasis. We then validated this signature in independent datasets using gene set expression comparison analysis with the LS-statistic.

A common metastatic signature of 79 genes was identified in the metastatic lesions compared with primaries with a False Discovery Proportion of less than 0.1. Interestingly, all the genes in the signature, except one, were significantly down-regulated, suggesting that overcoming metastatic suppression may be a key feature that is common to all metastatic tumors. Pathway analysis of the significant genes showed that the genes were involved in known metastasis-associated pathways, such as integrin signaling, calcium signaling, and VEGF signaling. To validate the signature, we used an additional six expression datasets that were not used in the discovery study. Our results showed that the signature was significantly enriched in four validation sets with p-values less than 0.05.

We have modified a previously published meta-analysis method and identified a common metastatic signature by comparing primary tumors versus metastases in various tumor types. This approach, as well as the gene signature identified, provides important insights to the common metastatic process and a foundation for future discoveries that could have broad application, such as drug discovery, metastasis prediction, and mechanistic studies.

Source: Meta-analysis of multiple microarray datasets reveals a common gene signature of metastasis in solid tumors. Daves Marla H., Susan G. Hilsenbeck SG, Lau Ching C., Man Tsz-Kwong ( BMC Med Genomics. 2011 Jul 7;4(1):56.

Les métastases sont la cause numéro un de décès par cancer. Les biopuces d'expression ont été largement utilisées pour étudier la métastase de divers types de cancer. Nous émettons l'hypothèse que la méta-analyse des ensembles, disponibles publiquement, de données d’expression de gènes dans les divers types de tumeurs peut identifier une « signature de métastase » commune à plusieurs types de tumeurs. Cette signature commune des métastases peut nous aider à comprendre les étapes « générales » du processus métastatique et d'identifier des biomarqueurs utiles qui pourraient prédire le risque métastatique.

Méthodes et résultats :
Nous avons identifié, dans la base de données Oncomine, 18 ensembles de données d’expression génique disponibles publiquement et comparant des métastases aux tumeurs primaires, et ce pour diverses tumeurs solides.
Une signature commune métastatique de 79 gènes a été identifiée dans les lésions métastatiques par rapport aux tumeurs primaires. Fait intéressant, tous les gènes dans la signature, sauf un, étaient nettement sous-régulés, ce qui suggère que le fait de surmonter une « suppression métastatique » peut être un élément clé commun à toutes les tumeurs métastatiques. L'analyse a montré que les gènes de la signature étaient impliqués dans des « voies moléculaires de métastases » connues : signalisation des intégrines, signalisation calcique, et signalisation du VEGF.

Nous avons modifié une méthode de méta-analyse publiées antérieurement et identifié une signature commune métastatique, en comparant les tumeurs primaires par rapport aux métastases dans divers types de tumeurs. Cette approche, ainsi que la signature génétique identifiée, fournit des renseignements importants sur le processus métastatique commun et représente une base pour des découvertes futures qui pourraient avoir une large application, tels que la découverte de médicaments, la prédiction des métastases, et les études mécanistiques.

Article (en anglais) librement accessible à l’adresse:

lundi 24 octobre 2011



Tumor types are classified according to the International Classification of Diseases for Oncology (ICD-O), 3rd Edition, World Health Organization, Geneva, 2000. The ICD-O-3 is a dual classification and coding system for both morphology and topography of a neoplasm.
The MORPHOLOGY code (Mxxxx/x) indicates the specific histologic term.
The TOPOGRAPHY code (C00-C80) is occasionally mentioned here.

Abbreviation: NOS, not otherwise specified


Les types de tumeurs sont classés en fonction de la « Classification Internationale des Maladies pour l'Oncologie (CIM-O), 3e édition, Organisation mondiale de la Santé, Genève, 2000. La CIM-O-3 est un système de classification et de codage pour la morphologie et la topographie d'une tumeur.
Le code de MORPHOLOGIE (Mxxxx/x) indique le terme spécifique histologique.
Le code de TOPOGRAPHIE (C00-C80) est occasionnellement mentionné ici.

Abréviation: SAI, sans autre indication




Craniopharyngioma, adamantinomatous
Craniopharyngiome adamantinomateux

Craniopharyngioma, papillary
Craniopharyngiome papillaire





Peripheral neuroectodermal tumor

Tumeur neuroectodermique périphérique

Askin tumor

Tumeur de Askin


Chordoma, NOS

Chordome, SAI

Chondroid chordoma

Chordome chondroïde

Dedifferentiated chordoma

Chordome dédifférencié