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Piri Welcsh on The Genetics of Breast and Ovarian Cancer, part of a collection of online lectures.

that is how the ‘two-hit hypothesis of cancer’ came into ..

In the hereditary form, most atypical ductal hyperplasia, ductal carcinoma-in-situ, children with an affected parent develop bilateral and invasive breast cancer as well as in normal ovary retinoblastoma; however, some develop unilateral and ovarian cancer.

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of breast and thyroid cancer: VHL:

The team led by Polyak and Michail Shipitsin, PhD, also of Dana-Farber and HMS, used gene activity analysis to clarify the relationship of the two cell types. They generated gene libraries from CD24+ and CD44+ cells purified from normal mammary epithelium and fluids within the chest, and from primary invasive tumor samples collected from breast cancer patients.

Patients treated with radiation therapy for acne (!) develop multiple skin cancers.

Recent studies examining the profile of genes expressed in tumors that metastasis to specific organs have identified specific genetic signatures of these tumors. For example, genes that mediate the metastasis of breast cancer to bone are different than those that mediate metastasis to the lung. In essence, different sets of genes allow tumor cells to specifically interact with the stromal cells of the target organ. These findings may lead to therapeutic strategies to target the metastatic properties of tumors.

It is now standard to stain paraffin sections of breast cancers with probes for erb-B2 (HER2/neu).


In 1971 he published his two-hit hypothesis of cancer ..

Instead, the scientists report in the March issue of Cancer Cell that they have identified two genetically distinct populations of cancer cells in samples of human breast tumors - one of the types being a cell recently proposed by other scientists to be a true breast cancer stem cell.

The Genetics of Breast and Ovarian Cancer | HSTalks

The results suggest that both cell types, and probably others, are involved in the development of breast cancer. While analyzing the genetics of each cell type, the researchers discovered that the proposed "cancer stem cells" were driven by an activated molecular pathway that makes them resemble normal stem cells. Women whose breast tumors are largely made up of these "stem-like" cells are at higher risk of recurrences.

Piri Welcsh on The Genetics of Breast and Ovarian Cancer, ..

On the positive side, the abnormal activated pathway in these cells, known as the TGF-Beta1 signaling pathway, can be blocked by experimental drugs now entering clinical trials, said Polyak, who is also an associate professor at Harvard Medical School. Such inhibitors, in combination with other therapies, may improve the prognosis in breast cancers fueled by these cells.

Neurofibromatosis type I with breast cancer: not only …

According to a longstanding cancer model, known as "clonal evolution," tumors arise from normal cells that mutate and generate abnormal offspring that also mutate, forming a mass of genetically varied cancer cells. However, there has been a new wave of interest in an alternative explanation - that tumors are initiated and driven by a single, abnormal type of adult stem cell found in, for example, breast tissue, resulting in a population of genetically identical tumor cells. Moreover, several pathways and genes required for normal stem cell function are activated in cancer cells and play essential roles in the development of tumors.

Neurofibromatosis type I with breast cancer: ..

In 2003, scientists purified what they proposed were breast cancer stem cells from patients' tumors. The distinctive molecule, or marker, on the cells' surface, known as CD44+, was identical to the marker on normal breast cells. When injected into mice lacking an immune system, the CD44+ cells demonstrated the ability to initiate breast tumors. The scientists also found closely related cells with a CD24+ marker and suggested that they were offspring of CD44+ cells.