Full-Exon Pyrosequencing Screening of BRCA Germline Mutations in Mexican Women with Inherited Breast and Ovarian Cancer

Full-Exon Pyrosequencing Screening of BRCA Germline Mutations in Mexican Women with Inherited Breast and Ovarian Cancer:


Hereditary breast cancer comprises 10% of all breast cancers. The most prevalent genes causing this pathology are BRCA1 and BRCA2 (breast cancer early onset 1 and 2), which also predispose to other cancers. Despite the outstanding relevance of genetic screening of BRCA deleterious variants in patients with a history of familial cancer, this practice is not common in Latin American public institutions. In this work we assessed mutations in the entire exonic and splice-site regions of BRCA in 39 patients with breast and ovarian cancer and with familial history of breast cancer or with clinical features suggestive for BRCA mutations by massive parallel pyrosequencing. First we evaluated the method with controls and found 41–485 reads per sequence in BRCA pathogenic mutations. Negative controls did not show deleterious variants, confirming the suitability of the approach. In patients diagnosed with cancer we found 4 novel deleterious mutations (c.2805_2808delAGAT and c.3124_3133delAGCAATATTA in BRCA1; c.2639_2640delTG and c.5114_5117delTAAA in BRCA2). The prevalence of BRCA mutations in these patients was 10.2%. Moreover, we discovered 16 variants with unknown clinical significance (11 in exons and 5 in introns); 4 were predicted as possibly pathogenic by in silico analyses, and 3 have not been described previously. This study illustrates how massive pyrosequencing technology can be applied to screen for BRCA mutations in the whole exonic and splice regions in patients with suspected BRCA-related cancers. This is the first effort to analyse the mutational status of BRCA genes on a Mexican-mestizo population by means of pyrosequencing.

How Much Weight Should Anecdotes Really Have In Health Policy?

How Much Weight Should Anecdotes Really Have In Health Policy?:
By D. Brad Wright

There’s something compelling about the personal narrative that vast mountains of quantitative data cannot rival. Anecdotes are, quite simply, powerful. They tap into our shared humanity, making something seem somehow more real by putting a face on it. This is why, if you follow politics for very long, you will find numerous cases of policymakers championing issues that have touched their own lives in some way. For example, Senator X doesn’t care about issue Y, until they discover that their son or daughter is affected by it. Then, almost overnight, they seem to care more about issue Y than almost anything else. Such a shift is completely understandable, but often out of proportion to the true scale of the issue in society.

In health policy, the personal narrative can also be very powerful. In fact, the journal Health Affairs routinely runs a “Narrative Matters” section that puts a face on the health care issues of the day. It is absolutely critical that health policymakers, health services researchers, and others, not lose sight of the fact that their work and the subsequent decisions it informs, are based on real people. However, it is equally critical for objectivity to be maintained, and narrative can threaten our work in this regard.......

Surgical site infection prevention: a survey to identify the gap between evidence and practice in University of Toronto teaching hospitals - Can J Surg. 2012 Jun 1

Blogger's Note: surgical site infections safety checklist: WHO (World Health Organization) program in patient safety

Surgical site infection prevention: a survey to identifythe gap between evidence and practice in University of Toronto teaching hospitals

 "Surgical site infections (SSIs) are the most common
complication following surgery, with reported rates
ranging from 5% to 30%.1 The attributable morbidity
and mortality is significant, with patients who experience
SSIs being 60% more likely to spend time in the
intensive care unit, 5 times more likely to be readmitted to
hospital and twice as likely to die than patients without
SSIs.2 Whereas many risk factors for the development of
SSIs are related to patient characteristics that cannot be easily
modified, there are a variety of system or hospital factors
that can be manipulated. These include improper selection
and administration of antibiotic prophylaxis, intraoperative
hypothermia and intraoperative hyperglycemia.3
Despite clear evidence and guidelines to direct SSI prevention
strategies, compliance is uniformly poor......

paywalled: The risk of metachronous cancers in patients with small-intestinal carcinoid tumors: a US population-based study

 Blogger's Note: while rare, and there is no specific reference in this abstract, carcinoid ovarian cancer tumors do exist so this research will be of interest for those diagnosed, this blog has some research on ovarian carcinoid tumors

The risk of metachronous cancers in patients with small-intestinal carcinoid tumors: a US population-based study

"In conclusion, almost one-third of patients with SICs have an associated metachronous primary tumor. When these primaries occur prior to (but not after) the SIC diagnosis, the prognosis is worse than with an initial SIC. The type of malignancies associated with SICs may guide future screening efforts.."

paywalled: Evolutionary Pathways in BRCAl-Associated Breast Tumors

Evolutionary Pathways in BRCAl-Associated Breast Tumors

Abstract

BRCAl-associated breast tumors display loss of BRCA1 and frequent somatic mutations of PTEN and TP53. Here we describe the analysis of BRCA1, PTEN, and p53 at the single cell level in 55 BRCA1-associated breast tumors and computational methods to predict the relative temporal order of somatic events, on the basis of the frequency of cells with single or combined alterations. Although there is no obligatory order of events, we found that loss of PTEN is the most common first event and is associated with basal-like subtype, whereas in the majority of luminal tumors, mutation of TP53 occurs first and mutant PIK3CA is rarely detected. We also observed intratumor heterogeneity for the loss of wild-type BRCA1 and increased cell proliferation and centrosome amplification in the normal breast epithelium of BRCA1 mutation carriers. Our results have important implications for the design of chemopreventive and therapeutic interventions in this high-risk patient population.

SIGNIFICANCE: Defining the temporal order of tumor-driving somatic events is critical for early detection, risk stratification, and the design of chemopreventive therapies. Our combined experimental and computational approach reveal that the loss of wild-type BRCA1 may not be the first event in the majority of BRCA1-associated breast tumors and may not be present in all cancer cells within tumors.  

Cancer Discov; 2(6); 1–9. ©2012 AACR.

Bionomics launches ovarian cancer trial - BNC105 Australia/U.S. (134 women/18 locations)

Bionomics launches ovarian cancer trial - clinical trials, cancer, Bionomics, Biotechnology - Australian Life Scientist

Bionomics (ASX:BNO) has launched a clinical trial of its BNC105 cancer treatment candidate in women with ovarian cancer.

The Phase I/II trial will involve up to 134 women across 18 sites in Australia, New Zealand and the US.

In Australia, the trial be conducted by the Australian and New Zealand Gynaecological Oncology Group in conjunction with the National Health and Medical Research Council Clinical Trials Centre.

Patients will receive BNC105 in conjunction with standard chemotherapy drugs carboplatin and gemcitabine......

Interval colon cancer in a Lynch syndrome patient under annual colonoscopic surveillance: a case for advanced imaging techniques? (including Lynch Syndrome background information/research)

 Blogger's Note: worth reading even for those without colorectal cancer but with a familial interest in Lynch Syndrome cancers, discusses research on surveillance timing, discordance in mutation carriers, risk variances (% risk) etc...

Background
Lynch syndrome confers increased risk for various malignancies, including colorectal cancer.
Colonoscopic surveillance programs have led to reduced incidence of colorectal cancer and reduced mortality from colorectal cancer. Colonoscopy every 1–2 years beginning at age 20– 25, or 10 years earlier than the first diagnosis of colorectal cancer in a family, with annual colonoscopy after age 40, is the recommended management for mutation carriers. Screening programs have reduced colon cancer mortality, but interval cancers may occur.

Lynch syndrome is defined as the presence of a germline mutation in a DNA mismatch repair gene [1]. Mutation carriers have increased risk for various malignancies, including carcinomas of the colorectum (CRC), endometrium, ovary, small bowel, stomach, biliary tract, bladder, ureter and renal pelvis [2].

Interval colon cancer in a Lynch syndrome patient under annual colonoscopic surveillance: a case for advanced imaging techniques?

"This report highlights several features of Lynch syndrome. First, individuals carrying deleterious mutations in a DNA mismatch repair gene (MLH1, MSH2, MSH6, PMS2) deserve annual colonoscopic examinations with a careful search for, and removal of, all mucosal lesions. Second, adenoma is the precursor lesion for CRC in Lynch syndrome.....

CancerGEM KB|Home - searchable database/online resource

Blogger's Note: see the results of the search using 'Lynch Syndrome' as a test per example below:

CancerGEM KB|Home


About CancerGEM KB
CancerGEM KB is a continuously updated searchable online resource that provides access to scientific information on the use of genomic information in cancer care and prevention. more

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Search CancerGEM KB




162 abstracts in HuGE published Literature

No GWAS/meta-analysis entry

1 evidence review/recommendation entries

1 genomic tests in transition to practice 

Office of Public Health Genomics/CDC launches the CancerGEM KB : CDC Office of Public Health Genomics in collaboration with NCI Division of Cancer Control and Population Sciences launches the CancerGEM KB: CancerGEM KB is an online resource for researchers, public health professionals, policy makers, and health care providers interested in the use of genomic information in cancer care and prevention. CancerGEM KB provides objective synthesis and timely dissemination of information on cancer human genome epidemiology (genetic associations, gene-environment interactions and gene prevalence information) and aggregated evidence on cancer genomic tests in transition to clinical and public health practice. CancerGEM KB also offers summary information on Genomic Tests through PLoS Currents Evidence on Genomic Tests, an open-access journal for systematic reviews and structured short summaries of evidence for the validity and utility of genetic tests. Read more about CancerGEM KB

 

Changing Roles and Responsibilities for Caregivers - free telephone workshop NCI June 19th

 The  Tenth Annual Cancer Survivorship Series:
Living With, Through & Beyond Cancer 

On Tuesday, June 19th, CancerCare, in collaboration with the National Cancer Institute: Office of Cancer Survivorship and Office of Communications and Education, LIVESTRONG, American Cancer Society, Intercultural Cancer Council, Living Beyond Breast Cancer and National Coalition for Cancer Survivorship, will present a free, telephone workshop entitled: Changing Roles and Responsibilities for Caregivers. You can listen to this program on the telephone or via live streaming through the internet.

This workshop is the third of a four-part series.  This free series is made possible by support from the National Cancer Institute and LIVESTRONG and offers cancer survivors, their families, friends and health care professionals practical information to help them cope with concerns that arise after treatment ends.   

The faculty for this program includes:

• Suzanne Martz-Dones, RN, MA, CCRN, NE-BC, Caregiver Perspective, Administrative Nurse Manager, Mount Sinai Hospital

• Barbara A. Given, PhD, RN, FAAN, University Distinguished Professor, Associate Dean for Research and Doctoral Program, College of Nursing, Michigan State University

• Stewart B. Fleishman, MD, Founding Director, Cancer Supportive Services, Continuum Cancer Centers of New York: Beth Israel & St. Luke's-Roosevelt

The fourth and final workshop of the series - Managing Post-Treatment Neuropathy - will take place on July 17th.  

These workshops are free – no phone charges apply.  However, pre-registration is required.  To register, and for more information, simply go to the CancerCare website, www.cancercare.org/connect.
If you missed Parts I or II of the series, they are available as podcasts, 24 hours a day, 7 days a week: 

Part I: Using Mind/Body Techniques to Cope with the Stress of Survivorship

Part II: Recapturing Joy and Finding Meaning
We are very excited to offer this telephone workshop series to you. We hope that you will join us and that you will share this information with your patients and colleagues.  

Old drug (Thioridazine) could have new use as cancer stem cell destroyer | CTV News

Old drug could have new use as cancer stem cell destroyer | CTV News

.....Thioridazine is known to work as a psychiatric and Parkinson's medication by targeting receptors in the brain for dopamine, which is a neurotransmitter that plays a variety of roles in the brain.
It turns out that leukemia cells (and other cancer types including ovarian) have a dopamine receptor on their surfaces too — making them vulnerable to the drug. The drug doesn't kill these cancerous stem cells, but rather encourages them to become normal again.
The team's research is published in the science journal, Cell.

.....The next step is to test thioridazine in clinical trials on cancer patients. The first study will focus on 30 patients with acute myeloid leukemia, or AML, whose disease has relapsed after chemotherapy.....

"By targeting the rare population of cells that seed, that drive the cancer, what we are hoping with the drug is to eliminate those cells and prevent patients from getting sick again," he says.

While researchers are excited, there are some concerns about side effects. Thioridazine was once widely used as a psychiatric medication, but its use has been curtailed after studies showed it can lead to heart and eye problems in patients taking it long term.
Health Canada took thioridazine off the market in Canada in 2005 after reports it could boost the risk of rare but potentially fatal changes in heart rhythm. Those problems happened only in patients who took the drug daily for more than two years. Bhatia says that for the cancer study, the drug would be used in low doses for about 20 to 30 days, much like standard chemotherapy.

A note of caution – many drugs that show effects in the lab may not work in people, so this is an exciting but very preliminary finding, say doctors.

Read more: http://www.ctv.ca/CTVNews/TopStories/20120524/thioridazine-cancer-drug-stem-cell-120524/#ixzz1vrcRskoW