Yes, that happened. A lawsuit against Myriad BRCA patents in USA. The plaintiffs include Breast Cancer Action, The American College of Medical Genetics, the Association for Molecular Pathology, the College of American Pathologists, the American Society for Clinical Pathology, individual researchers, patient advocacy groups, genetic counselors, and individual women. Hey guys, I am with you!

The monopoly that Myriad Genetics now enjoys (at least in USA) due to these patents reduces consumer choice and removes the competitive incentives regarding price, quality assurance, or improvement of the tests (just remember the case with large scale deletions which previous  Myriad tests just missed before 2002). In my opinion human gene patents are intrinsically flawed – you can patent a technology and tools (e.g. test) but not a (natural) sequence.

In Europe there was (and still is) strong opposition against Myriad monopoly (alas this year they infringed patents for commercial use in largest European countries).

For those overseas – there are more cheaper testing options available via dedicated networks, like Gendia or Diagnogene.

Today is an international Von Hippel Lindau Disease Day. VHL Alliance is the main source of information about this disease and also very active community. Take a look at VHLA Youtube channel.

Von Hippel Lindau is a rare (1:35000) autosomal dominant genetic condition with increased formation of specific vascular tumours (mostly benign) called hemangioblastomas, mostly in eye retina and cerebellum as well as increased risk for renal clear cell carcinomas at young age and sometimes adrenal pheochromocytomas. Multiple pancreatic and renal cysts are common.

(image from a very informative article in Lancet, 2003)

The critical management step is an early recognition of VHL with the help of genetic testing what allows presymptomatic  identification of persons at risk and target them towards specific surveillance and prompt treatment.

Molecular testing is quite easy – VHL gene has only 3 exons which can be easily sequenced for small mutations. But there is a trick: up to 30-40 percent of mutations are large deletions of entire gene or particular exons, therefore other techniques must be used, like MLPA or real-time PCR. Altogether nearly 100% sensitivity can be reached.

Each case of hemangioblastoma, renal clear cell carcinoma (RCC) or pheochromocytoma before the age of 50, bilateral or multifocal involvement should prompt to genetic testing.

There are lot of efforts for developing targeted cure for VHL – anti-VEGF therapy is one experimental choice. Hopefully other strategies (like modulation of HSPC300 gene activity) will bring some hope for a cure.

On monday I’m organising VHL seminar for doctors at our hospital  as well as bringing VHL patients together.

I am back. 2008 were quite important for me – graduated clinical genetics and virtually shifted from traditional-pediatrics based genetics and focused solely to cancer and adult onset disease, also half-sunk in molecular lab – working in best equipped lab with cool people is great. This month will try to handle pyrosequencing and Illumina genotyping, wow.

And defented my long-rolled PhD in tumor cell kinetics and T regulatory cells (enjoy the power of Open Access).

Do you know that 4154delA mutation of BRCA1 gene seems to originated in the Eastern Baltic Sea region of the Northern Europe? Read my and colleagues articles.

Research is the best way to find new health improving strategies. Such example could be  CIMBA -  “Consortium of Investigators of Modifiers of BRCA1/2″) – an international initiative to identify genetic modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers. The goal is to find SNPs which could be important in modifing BRCA mutation effects and thus important in clinic for correct genetic risk stratification. A newly formed Baltic Familial Breast Ovarian Cancer Consortium (BFBOCC) currently is activelly recruiting patients from Lithuania and Latvia for the involvement in CIMBA (contact person for LT – me).

Spare time (hm, a night:) is a good for website developing – www.genetika.lt – is my new website in constant progress in lithuanian language to help translate cancer genetics in understandable manner for patients and doctors. This lovely header is creation of this weekend with the genuine help of Gimp buddy:

Von Hippel-Lindau (VHL) disease – a rare tumor predisposing disorder, where targeted surveillance and early diagnostics is crucial for the improved patients survival – is no longer an  “incognito” in my country – developed genetic testing and counseling service will help for these families to get the best from current medical practice. More about VHL.

And for 2009 several new genetic testing are scheduled to come – Familial Adenomatous Polyposis, Multiple Endocrine Neoplasia syndrome (type I and II), Neurofibromatosis type II and Li-Fraumeni syndrome – developing National Hereditary Childhood Cancer Research Platform.

Thats for now – greetings from Vilnius, European Capital of Culture 2009.

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Familial Cancer Database Online is a very useful online tool for experts in cancer genetics to assist in making a genetic differential diagnosis in cancer patients as well as remind tumor spectrum associated with certain hereditary disorders.

And its dynamic cyberinfrastructure already brings the most updated content in the field of clinical cancer genetics with intention to develop further.

The content was created and is edited by dr. Rolf Sijmons (on the left – during poster presentation at ESHG meeting in Barcelona this year), clinical geneticist and associate professor clinical oncogenetics at the Dept. of Genetics of the University Medical Center Groningen (UMCG), the Netherlands. However, other experts who want to contribute to particular syndrome files are invited to contact the editor; these authors will be listed in the syndrome files they contributed to.

And I’m pleased of being included in the list of contributors for the contribution to rare hereditary disorder called Mosaic Variegated Aneuploidy syndrome, where in addition to other symtomes the risk for several cancers (leukemia, rhabdomyosarcomas and embrional kidney cancers) is increased.

FaCD is intended for free of charge use by health professionals with at least basic knowledge of clinical cancer genetics.

This is an exciting time in the study of hereditary factors involved in breast cancer susceptibility. Breast cancer for a long time was classified according histology. Now genetics play a significant role and better knowledge ensures better management and treatment.

Hereditary breast cancer (HBC) accounts for as much as 10% of the total BC burden. Only about 30 percent of these cases will be found to be due to a germline mutations in well known BRCA1 and/or BRCA2 genes, but the rest won’t have these mutations. Less than 10 percent of remaining HBC will fall into other rare conditions – and here we can see breast cancer as heterogeneous disease (ref.):

Cowden, Li-Fraumeni syndromes, heterozygosity for Ataxia telangiectasia-mutated gene (ATM) or for CHEK2 1100delC or other rare conditions Nijmegen breakage syndrome (NBS1), familial diffuse gastric cancer (CDH1), Peutz-Jeghers syndrome (STK11), Fanconi anemia (BRIP1, PALB2), Bloom syndrome (BLM)) contribute sligthly – there is consensus for ten most important genes involved in HBC (ref.)

An estimated additional 15–20% of those affected with BC will have one or more first- and ⁄ or second-degree relatives with BC (familial or polygenic breast cancer). Therefore, when these numbers are combined, familial BC risk accounts for approximately 20–25% of the total BC burden (see figure).

Here we’re talking about so called low-penetrance susceptibility genes and variants (SNPs), like rs2981582 in FGFR2, rs889312 in MAP3K1, rs3803662 in TNRC9, rs1801270 in CASP8 and many more, most of which were hot topics in the recent years. Particular alleles (particular “letter” variants of these digitalized “rs” SNPs) only increase risk slightly (twice or so) and are intense study object now, but they sooner or later will enter clinical practice.

This week I was really happy to meet the founder of SNPedia Mike Cariaso. And not virtually, but in reality in my native city Vilnius, where a bioinformatics EuroPhyton conference was held. Some walk in the old town and beer was great. And there was even famous Hans Rosling talk in this conference! (what a pity, I didn’t manage to listen to it, but it was pretty much the same he had at TED conference:

If you do not know what is SNPedia – it is collaborative aggregation of information about genetic variation, inspired by the personal need to understand own variation (Mike has done own SNP scan on two platforms).

This website shares information about the effects of variations in your DNA, citing peer-reviewed scientific publications. Great stream from Bethesda, MD, just opposite National Health Institute:)

And there is something unique in Vilnius, a blend of American (unnoficial) culture – the monument of Frank Zappa – the only such kind of monument for rock musician in a world.

Zappa’s death from prostate cancer in 1993 hit photographer Saulius Paukštys and fellow devotees hard and in a flash of inspiration they managed to erect a lasting memorial to this truly libertarian person.

Just wrote some notificaion on commercial tests in my “genetic testing” section:

IMPORTANT NOTE. Some commercial tests for moderate/low cancer risk genetic predisposition are not verified/supported by independent experts or scientific evidence. Please consider these links with common sense and vigilance.

Take care:)

As for clinical geneticist, traditionally concerned more with germline (hereditary) mutations and disease, it might be strange to search through somatic mutation (or acquired) databases. But it is obvious that understanding of cancer genetics can not be limited to only germline or somatic mutations – it must be combined approach. And then you start to think in systemic way, or in other words, you think in pathways or patterns (pretty much the same way as main character from D. Aronofsky’s notorious “Pi” )

Anyway, currently I’m gliding through Ras-MAPK signaling pathway and in a future some posts will be related to it. Interestingly, lot of things in genetics are connected or in other ways, as a friend of mine once stated, “traditional genetics is dead”

Just take a look: Ras-MAPK pathway is probably one of the most upregulated pathway in sporadic cancers. And there are bunch of syndromes with inherited altered mutations in a genes from there:

Among other symptoms, Neurofibromatosis type 1 have up to 13% risk for developing maligancy (mostly for MPNST), Costello syndrome have about 17% increased risk of cancer (particularly rhabdomyosarcomas, neuroblastomas and bladder Ca), in Noonan there is increased risk for juvenile myelomonocytic leukemia. Therefore lot of attempt must taken to perform targeted screening for these patients. LEOPARD (which is allelic for Noonan s. and stands for lentigines, ECG anomalies, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, retarded growth and deafness) and CFC syndrome seems do not have increased cancer risk.

For somatic mutation in cancer invaluable tool seems to be COSMIC database – Catalogue of Somatic Mutation In Cancer by Wellcome Trust institute. COSMIC is designed to store and display somatic mutation information and related details and contains information relating to human cancers. Enjoy.

Apologize for such long silence – was finishing my residency. And it is done – already received MD (clinical genetics). Now searching for the best way to practically realize my interest in familial cancer genetics – and to set up service which is virtually non existent in Lithuania.  Hopefully, July will bring what I wish and move to a new working place, which will be more creative and simply better.

Happy DNA day! This year in Europe we celebrate it for the first time officially. What a coincidence – yeasterday I’ve received gene T-shirt with mapped 1st chromosome from the magazine Science – wearing it all this day:)

On this occasion I would like to introduce you to SimpleGenetics(TM) genetic test reviews – it could be an independent wiki-based resource dedicated to the provision of reviews and unbiased information about commonly available genetic tests, its clinical validity and utility.

The project aims to improve the quality and accessibility of information regarding genetic tests and help to make informed choice decision for physicians and/or patients.

The information would be reviewed and edited by registered clinicians or scientists working in clinical genetic settings.

There is a preference for objective, scientific evidence-based, comprehensive reviews of clinical evidence and appreciate contribution of both genetic testing companies, clinicians and users to satisfy these goals.

I made this draft in February, and there is some information about Mammaprint available already. Let me know what you think about it and future involvement/contribution/etc. possibility.

Check out at SimpleGenetics.com