Egg genome is reprogrammed to match to the semen with or without a paternal genome

Main Category: Cancer / Oncology
Also Included In: Biology / Biochemistry;??Genetics
Article Date: May 2013 13 - 1:00 PDT Current ratings for:
Egg Genome Is Reprogrammed To Match Sperm's With Or Without A Paternal Genome

Researchers from Huntsman Cancer Institute (HCI) at the University of Utah have discovered that while the genes provided by the father arrives at fertilization pre-programmed to the state needed by the embryo, the genes provided by the mother are in a different state and must be reprogrammed to match. The findings have important implications for both developmental biology and cancer biology.

In the earliest stages, embryo cells have the potential to develop into any type of cell, a state called totipotency. Later, this potency becomes restricted through a process called differentiation. As a result, as cells continues to differentiate, they give rise to only a subset of the possible cell types.

"In cancer, normal processes of cell differentiation and growth go wrong, and cells either become arrested at an early state of differentiation, or instead go backwards and are 'reprogrammed' to become more like early embryo cells," said Bradley R. Cairns, co-author of the article and Senior Director of Basic Science at HCI. "By understanding how cells are normally programmed to the totipotent state, and how they develop from totipotent that state into specific cell types, we hope to better understand how cancer cells misregulate this process, and to use that knowledge to help us currency strategies to reverse this process." The research results were published online as the cover story in the journal Cell.

Earlier work in the Cairns Lab showed that most genes important for guiding the early development of the embryo are already present in human sperm cells of the father in a "poised" state - turned off, but with attached markers that make gene activation easy. "The logic is that all the important decision-making genes for early development are ready to go," said Cairns. "This poised state is never seen in fully differentiated cells such as skin cells."

In the current study, researchers in the Cairns Lab used high-throughput gene sequencing to dafcomprehensively and precisely analyze DNA methylation patterns in the genomes of zebrafish, which is a common laboratory model both for developmental and cancer biology. Here, they examined egg cells, sperm cells, and four phases of embryonic development: three phases between fertilization and when the embryo's genome becomes active, and one phase after that point. Methylation - in which molecules called methyl groups are selectively attached to certain areas of the DNA and turn off gene activity in those areas - is one of the main markers of gene poising. poised genes lack DNA methylation, enabling gene activity later in embryo development.

Cairns' group found that the methylation pattern of the soon-to-differentiate embryo is identical to that of the sperm cell. In contrast, the pattern of the egg cell was initially quite different, but undergoes a striking set of changes to become exactly matched to that of the sperm DNA. Cairns' work suggests that egg DNA goes through this extensive reprogramming to prepare for the process of differentiation.

"The maternal genes that underwent DNA methylation reprogramming are among the most important loci for determining embryo development," said Cairns. "For example, many hox genes, which determine the body plan and also differentiation during hematopoiesis [the formation of blood cells], are methylated in the mother's genetic contribution and demethylated in the father's, and therefore, also in the embryo."

He said the work added another interesting finding. "We found that the mother's genome takes care of that remodeling on its own, without using the father's genome as a template." Cairns' experiments showed that when the father's genetic contribution was removed, the mother's genome still remodeled itself to the correct state.

"Basically, we re trying to understand how a single cell can make a decision to be any type of cell," said Cairns. "It is a fascinating fundamental question in biology that has implications for all aspects of development and many aspects of diseases such as cancer."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our cancer / oncology section for the latest news on this subject. Cairns is a Howard Hughes Medical Institute investigator, a Huntsman Cancer Institute investigator and a professor in the Department of Oncological Sciences at the University of Utah. He also holds a Jon and Karen Huntsman Presidential Professorship in Cancer Research. Potok is a doctoral candidate in the Cairns Lab at HCI. Co-authors David Nix, PhD, and Timothy Parnell are also affiliated with HCI. Nix is a research assistant professor in the Department of Oncological Sciences at the University of Utah, and Parnell is a research associate in the lab of Cairns.
This work was supported by the Howard Hughes Medical Institute, the Huntsman Cancer Foundation, and NCI CA24014 (for core facilities).
University of Utah Health Sciences Please use one of the following formats to quote this article in your essay, paper or report:

MLA

University of Utah Health Sciences. "Egg Genome Is Reprogrammed To Match Sperm's With Or Without A Paternal Genome." Medical News Today. MediLexicon, Intl., May 13. 2013 Web.
May 13. 2013 APA

Please note: If no author information is provided, the source is cited instead.

'Egg Genome Is Reprogrammed To Match Sperm's With Or Without A Paternal Genome'

Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.

If you write about specific medications or operations, please do not name health care professionals by name.

All opinions are moderated before being included (to stop spam)

Contact Our News Editors

For any corrections of factual information, or to contact the editors please use our feedback form.

Please send any medical news or health news press releases to:

Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.

View the original article here

Lumpectomy without Radiation an Option for Some Older Breast Cancer Patients

Among women aged 70 or older with Stage I, estrogen receptor-positive breast cancer, treatment with lumpectomy and tamoxifen resulted in a higher rate of cancer recurrence but similar overall survival as treatment with lumpectomy, tamoxifen, and radiation therapy. These results, which will be presented at the 2010 annual meeting of the American Society of Clinical Oncology, suggest that some older women may be able to forego radiation therapy without adversely affecting survival.

Surgery for early-stage breast cancer typically involves either mastectomy or lumpectomy. A mastectomy involves removal of the entire breast, whereas a lumpectomy involves removal of the cancer and a portion of surrounding tissue.? Because a lumpectomy alone is associated with a higher rate of cancer recurrence than mastectomy, patients who elect to have a lumpectomy are generally also treated with radiation therapy. The combination of lumpectomy and radiation is called breast-conserving therapy. Studies have shown that breast-conserving therapy is associated with a lower risk of local cancer recurrence than lumpectomy alone.

Although the addition of radiation therapy to lumpectomy reduces the risk of local cancer recurrence, radiation therapy typically takes place over several weeks and requires a large commitment of time from the patient. This has prompted interest in whether there are certain groups of women with early breast cancer who can safely forego radiation therapy after lumpectomy.

The current study involved 636 women aged 70 or older with Stage I, estrogen receptor-positive breast cancer. After lumpectomy, women were assigned to additional treatment with tamoxifen alone or tamoxifen plus radiation therapy.

Women have now been followed for over 10 years.

The risk of cancer recurrence in the same breast was lower among women who received radiation therapy: a local cancer recurrence developed in 2% of women treated with tamoxifen and radiation therapy and 8% of women treated with tamoxifen alone.Breast cancer-specific and overall survival were similar in the two study groups: 10-year overall survival was 61% among women treated with tamoxifen and radiation therapy and 63% in women treated with tamoxifen alone.

These results suggest that among older women treated with lumpectomy and tamoxifen for Stage I, estrogen receptor-positive breast cancer, skipping radiation therapy increases the risk of local cancer recurrence but does not adversely affect overall survival.

Older women with early breast cancer may wish to talk with their doctor about the risks and benefits of all treatment options.

Reference: Hughes KS, Schnaper LA, Cirrincione C et al. Lumpectomy plus tamoxifen with or without irradiation in women age 70 or older with early breast cancer. To be presented at the 2010 annual meeting of the American Society of Clinical Oncology. June 4-8, 2010. Chicago, IL. Abstract 507.

View the original article here

A BRCA Gene Mutation in the Family Does Not Increase Cancer Risk for Those Without the Mutation

For women who do not have a BRCA1 or BRCA2 gene mutation, having a close relative with one of these mutations does not increase breast cancer risk. These results were published in the Journal of Clinical Oncology.?

Inherited mutations in two genes—BRCA1 and BRCA2—have been found to greatly increase the lifetime risk of developing breast and ovarian cancer. Mutations in these genes can be passed down through either the mother’s or the father’s side of the family.????

Women who test negative for a BRCA gene mutation—but who have family members with a mutation—are generally thought to have a risk of breast cancer that’s similar to that of women in the general population. A study published in 2007, however, raised concerns that relatives of BRCA mutation carriers may have a substantially increased risk of breast cancer even if they test negative for their family’s mutation.[1]?

To further explore cancer risk among close relatives of people with BRCA mutations, researchers conducted a study among more than 3,000 families with at least one case of breast cancer; 160 families had a BRCA1 mutation and 132 families had a BRCA2 mutation.[2]?

For women without a BRCA mutation, breast cancer risk was similar whether or not the woman’s family had a BRCA mutation. These results suggest that coming from a family with a BRCA1 or BRCA2 gene mutation does not increase cancer risk for those who test negative for the mutation.?????

Although this is reassuring news, women who test negative for their family’s gene mutation should continue to follow cancer screening guidelines. These women do not have the very elevated cancer risk that their affected relatives have, but they can still get cancer.???

References:?

Posted November 9, 2011

[1] Smith A, Moran A, Boyd MC et al. Phenocopies in BRCA1 and BRCA2 families: evidence for modifier genes and implications for screening. Journal of Medical Genetics. 2007;44:10-15.?

[2] Kurian AW, Gong GD, John EM et al. Breast cancer risk for noncarriers of family-specific BRCA1 and BRCA2 mutations: findings from the Breast Cancer Family Study. Journal of Clinical Oncology. Early online publication October 31, 2011.?

View the original article here