Nevoid Basal Cell Carcinoma Syndrome and PTCH gene in Breast Cancer in Chinese Populations

Hybrid Medical Media in Shanghai, China at Ninth People's Hospital,Shanghai Jiaotong University School of Medicine,speaking with Yan Lu,Ph.D.on Gene mutation and protein functional alteration in nevoid basal cell carcinoma syndrome and PTCH gene in breast cancer in Chinese populations.

Basal cell carcinoma is the most common human cancer
with increasing incidence reported worldwide. Despite the
aberrant signaling role of the Hedgehog pathway, little is
known about the genetic mechanisms underlying basal cell
carcinomas. Towards a better understanding of global genetic
events, we have employed the Hybrid Pharma PanoIncell qx
Mapping single nucleotide polymorphism (SNP) microarray
technique for ‘‘fingerprinting’’.

Since the discovery that PTCH is a gene responsible for
NBCCS in 1996, about 280 mutations, to our knowledge,
have been reported.

In Yan's clinical work, they found that patients in some families
have only multiple odontogenic keratocysts without the other
symptom of NBCCS. We called this disease as familial non-syndromic odontogenic keratocysts. Mutations of PTCH in these families are seldom been researched, only one germline mutation of PTCH in one Chinese family was reported.

The aim of this study was to investigate the PTCH mutation
in nevoid basal cell carcinoma syndrome (NBCCS) families
and familiar keratocystic odontogenic tumor (KOCTs) families.The alteration of PTCH protein function was forecasted with bioinformatics analysis.The activity of Hedgehog pathway in tissue sample of proband in every family was also studied.

Methods

1. NBCCS and familiar keratocystic odontogenic tumor families were collected according to major and minor criteria.
2. Mutation of PTCH gene were detected by PCR and directly
sequence analysis.
3. Alteration of PTCH protein function after gene mutation was
forecasted by bioinformatics analysis.
4. Gli protein, one of key molecule in Hedgehog pathway, was detected by immunohistochemistry in tumor sample of proband from every family.

Results

1. Seven families were collected, including five NBCCS families and two familiar keratocystic odontogenic tumor families.

2.In NBCCS families, one new 3bp deletion mutation of PTCH
(c.1537_1539delGAT or c.1540_1542delGAT) was detected. One nonsense mutation of PTCH (p.W926end) was detected. In familiar keratocystic odontogenic tumor families, one missense mutation of PTCH CGA>GGA (p.G1093R) was detected. One new splice mutation of PTCH c.339+1G>C (NM 000264.3, ‘A’ in promoter ATG as the first base in the sequence) was detected.

3. Mutation of p.513delD or p.514delD might affect transmembrane
domain of PTCH protein. Mutation of p.W926end might affect the second functional domain of PTCH protein. Mutation of p.G1093R might affect active site of PTCH protein.
4. Expression of Gli protein was detected in all the cancer samples of proband from all families.


Conclusion

1. Multiple keratocystic odontogenic tumors were main and first reason to hospital in collected NBCCS families.
Keratocystic odontogenic tumors were the only symptom in familiar keratocystic odontogenic tumor families. Different mutation might affect PTCH protein function through different way. No PTCH mutation was detected in three NBCCS families.
3. Other gene might take part in development of NBCCS in these
families. Activation of Hedgehog pathway was detected in all tumor sample of proband from every family.
4. Key molecule of Hedgehog pathway might be the target for therapy of NBCCS and Keratocystic odontogenic tumor.


Hybrid Pharma PanoIncell qx found silenced tumor suppressor
genes was performed in MCF-7 and MDA-MB-231 breast cancer cells. Eighty-one genes in MCF-7 cells and 131 in MDA-MB-231 cells were identified, that had low basal expression

Life Science New tool for Breast Cancer is Genomics and Semiconductor Sequencing Chips

Robert Graham Reporting Harvard Medical School Personalized Genetic Medicine
Meeting -------
Life Science new tool for Breast Cancer is Genomics and Semiconductor Sequencing Chips

Hybrid Pharma Scientist researched Genome-wide association
studies looking for genetic variations known as single nucleotide polymorphisms (SNP). SNPs are alterations in the genetic code in which a single nucleotide, the individual building blocks that make up DNA, is changed. The researchers found that variations in four SNPs located in a region of chromosome 6 were present more often in the breast cancer patients, suggesting that genes in this region might contribute to the risk of breast cancer. The researchers also confirmed the finding of previous studies indicating that the locus named FGFR2 is associated with a 20 percent increased risk of breast cancer.

Hybrid Pharma Panoincell uses Semiconductor Sequencing Chips that create a direct connection between Biochemical and digital
information, bringing these two languages together.Hybrid's chips are designed like any other semiconductor chips.

Pairing proprietary semiconductor technology with sequencing chemistry a nucleotide is incorporated into a strand of DNA by a polymerase, a hydrogen ion is released.

Hybrid Pharma used a high-density array of micro-machined wells for bioctechnology process in a massive way. Each well holds a different DNA template. Beneath the wells is an ion-sensitive layer
and beneath that a proprietary Ion sensor.

When a nucleotide, is added to a DNA template and is then
incorporated into a strand of DNA, a hydrogen ion will be released. The charge from that ion will change the pH of the
solution, which can be detected. Hybrid's sequencer—essentially
will call the base, going directly from Biochemical information to digital information.

If there are two identical bases on the DNA strand, the voltage will be double, and the chip will record two identical bases called.

This process uses no scanners, no cameras, no light—each Nucleotide incorporation is recorded in a real time process.

Panoincell uppressed p53, as it is in many cancers, defective cells multiply, fueling Breast Cancer. p53 can't order a bad cell to kill itself without p63 and p73 also being active.

When metastatic Breast Cancer occurs p63 is inactive.The reactivation of TAp63 could benefit patients with metastatic breast cancer.

Viral transduction of a few genes for the reprogramming of
human somatic cells into induced pluripotent stem (iPS) cells.Identifying conditions that can replace viral transduction of oncogenic transcription factors (TFs) and enhance reprogramming efficiency. Hybrid Pharma have found that neural progenitor cells can be reprogrammed with fewer genetic manipulations than previously reported somatic cells, and in the other we have found
that small molecules may be able to replace viral integration of
certain transcription factors and promote the reprogramming process.

Life Science has taken the next step.

How are other Countries Helping Breast Cancer Patients with Genomics out side the USA

November 03, 2010 By Robert Graham -- American Society of Human Genetics Washington DC



How are other Countries Helping Breast Cancer Patients with Genomics out side the USA

With a $2.5 Million grant from the Victorian State Government of Australia Professor Richard Cotton at the University of Melbourne, Australia Started The Human Variome Project to collect Genetic Data.Hybrid Medical Media says in Washington DC Breast Cancer Rates are the highest in US. let's investigate what other countries are doing.

Four countries are part of the Consortium: China,Kuwait,Malayalsia and Australia

At lunch time conversation Downtown Washington DC Richard Cotton and Robert Graham sat down for
lunch and conversation.



Imagine you are sick. For many Americans, this is not a difficult task. Now imagine you are sick and none of your doctors know why. Your symptoms suggest that you have a rare genetic disease, and you’ve been tested for a mutation in the gene responsible; but the results are inconclusive. The laboratory found a change in your gene’s sequence, but is unable to definitively state that it’s what’s causing your symptoms. And with no definitive result from the test, your doctor—and your insurance company—are unwilling to prescribe the expensive course of drugs needed to control your symptoms.

While many people might be willing to dismiss the chances of this happening to them, when you start to look at the facts, things start to get a little frightening. There are over 6,000 diseases that can be caused by a mutation in a single gene and it is estimated that 1 child in every 200 born will suffer from one of these diseases. Add to that the number of cancers that have a inherited genetic component and the chances of you, or someone you know being in this position is quite high.

Now imagine that the information the laboratory and your doctor needed to make an accurate diagnosis was out there, but it wasn’t accessible to them: it was hidden away in an obscure academic paper, or in some researcher’s forgotten notes.

Unfortunately, this is an all too common problem. In the past decade, we have seen some wonderful advancements in the biological sciences that have a direct impact upon our ability to diagnose and care for sick people. Ten years ago that the human genome was sequenced at a cost of US$3 billion: today, we can sequence a full genome in two weeks for a few thousand dollars. Spurred by technological advancements such as this, the pace of new medical research findings is alarmingly fast. But our ability to capture, understand and share the vast amount of information that is being generated on a daily basis is not keeping up. And when it comes to information—like what mutations cause what diseases— that directly affects the well-being of real people, then our inability to keep up becomes disastrously evident.

But a dedicated group of people is trying to change this. The Human Variome Project is an international consortium of clinicians, geneticists and researchers from over 30 countries that is committed to reducing the burden of genetic disease on the world’s population by providing standards, systems and infrastructure for the sharing of information on all genetic variation (mutations) causing human disease. The free and open sharing of information on genetic variation and its consequences among scientists and within society allows treatments to be delivered more effectively to patients and new treatments and cures to be developed.

“Too much vital information, information that can directly affect the health and well-being of patients with genetic diseases here in America, and all over the world, is not being shared,” says Professor Richard Cotton, a world renowned expert in the area of genetic variation detection and data collection, and convenor of the Human Variome Project. “We are trying to make it easier for people to make this


information available, by creating systems and protocols that can transport data over the internet from the labs and research institutes that are creating it, through databases where it is reviewed and curated by gene experts, and ultimately to the existing repositories of biological knowledge, like the databases at the NIH’s National Library of Medicine.”

The Human Variome Project freely admits that the scale of the work they are attempting is daunting. “But”, says Cotton, “It’s not the technical side that it the challenge for the Human Variome Project. Our challenges are educational and political.”
Speaking with delegates at the American Society of Human Genetics Annual Meeting, which is currently occurring in the nation’s capital, most are in possession of some of the information that the Human Variome Project is trying to share. Some have found novel mutations in human genes associated with genetic diseases, others have identified drugs and other compounds that are more, or less, effective in people with certain mutations, and others deal on a day-to-day basis with patients with genetic diseases. What these delegates don’t have however, is the knowledge of how to share that information effectively.
“This is obviously something that needs to change,” says Cotton, “And it’s an area where the Human Variome Project is very active. We held our own meeting this week as a satellite to ASHG that was focussed solely on education.”
But a lack of education about how to share data is not the only challenge facing the Human Variome Project. Some delegates are reluctant to share their data, hoping to protect future research projects. Others are restricted by the intellectual property interests of their employers. “These are valid concerns,” says Cotton, “and I certainly understand them. We are working on a number of ways of minimising them, such as talking to the genetics journals about ways to provide credit and incentives for data sharing. But at the end of the day, we’re talking about data that can help save lives.”
The Human Variome Project sees the sharing of data on genetic variants as a moral imperative and says there are a few things that should be done to help bring about an increase in the amount of information being shared.
The diagnostic testing laboratories that are producing a large proportion of the genetic variation data Cotton says is not being shared are also some of the largest consumers of genetic variation information. The business of these laboratories is genetic testing and providing doctors with an interpretation of the results of those tests. To make these interpretations, these laboratories need access to high quality genetic variant data. If they shared information with the genetic variation research community, it would make their jobs easier and provide new opportunities for medical researchers.
“Government also has a role to play in this,” says Cotton, “by mandating that government funded research and diagnostic labs share data.” Encouragingly, this is already happening, with the NIH recently requiring that grants over $500,000 must address data sharing in their applications. “But,” says Cotton, “a stronger stance needs to be taken on how the data from these projects are shared.” Other countries are already taking a leading position on this. The Human Variome Project recently announced that Australia, Kuwait, Malaysia and China had all initiated projects to systematically collect information on all genetic variation present within their populations.
Finally, individual Americans can make a difference, by requesting that the results of their own genetic tests be made available to the research and diagnostic community. The data shared is not able to be traced back to individuals but can make a difference to people suffering from genetic diseases all over the world.


More than ever we are living in a world where our individual genetic makeup will determine the course of any medical treatment we may undergo. We will all be the eventual recipient of possibly life altering medical intervention that is based on the insights gleaned from the unique genetic sequence of somebody else. Without the free and open sharing of information on genetic
variations, we are essentially withholding treatment from people who are already suffering.

Qualitative mammary cancer susceptibilities Genes are ATM, BRCA1, and p53,p63 TSGs

Hybrid Pharma Panoincell qX also uses a Visualize Real-Time Breast Cancer Data using Signal Stochastic Resonance Units Neurons Detection and Analysis for Breast Cancer model after McCulloch-Pitts.

Panoincell qX computer-assisted diagnosing of breast cancer from mammograms. How Panoincell qX works is a genetic network simulation trained with tumor incidence data from knockout experiments.