Often, finding the gene(s) that cause a disease is like the proverbial needle in a haystack. And in very rare cases, it’s Pleuropulmonary blastoma (PPB) is a rare childhood lung cancer where cysts and/or solid tumors grow in the lungs of children anytime from birth to about 7-8 years of age.

Malignant cancer cells. Image: Newscom

Only about 50% of patients with PPB are successfully cured of the cancer, and the prognosis becomes better with early diagnosis. One fourth of children with PPB have other types of cancers in their bodies (personal history) or in other family members, so there is a clear genetic factor involved.

A recent study found very interesting results that could help scientists understand how cancers develop. Results from a molecular study found that that a master controller gene called DICER1 was responsible for PPB. A mutation in the DICER1 gene will cause the expression of other genes to go out of control. And somehow, DICER1 deregulates those signals to nearby cells and turns those cells malignant. However, the cells with the mutated gene do not turn malignant. It’s really very interesting because it explains how other types of cancers are also found in children with PPB.

The International PPB Registry has links to the study abstract presented at the 100th Annual American Association of Cancer Research.

via PRNewswire

A new genetic syndrome was discovered in a group of families in Quebec with a common ancestor. The syndrome was named MEDNIK to describe the resulting phenotypes - mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratodermia.

The scientists found a new splice mutation in the AP1S1 gene, which encodes a subunit of a complex (AP) responsible for selecting which proteins move within the cell. A zebrafish knockdown model was used to study the loss of the gene’s function further. Injecting the affected larvae with a human normal AP1S1 mRNA restored some phenotypes.

The study is published in PLOS Genetics.

The cold and short days of winter usually make people eat and sleep more. Some may even have cabin fever or claustrophobia from being indoors most days. These are normal reactions for most of us during the fall to winter season. However, a person who suffers from seasonal affective disorder may experience more serious reactions than just the "winter blahs".

A severe type of depression, seasonal affective disorder (SAD) affects about 6 percent of the US population. The symptoms and mood changes can be devastating, and come back year after year. It is usually treated with a light therapy where a SAD patient is exposed to bright light in the mornings to trick the brain into believing that the days are longer.

A new study  finds a mutation in the melanopsin gene makes a SAD patient require more light to function normally.  Melanopsin is a photopigment that helps regulate circadian rhythms and other non-visual responses in the eye. An individual with two copies of the mutation in the melanopsin gene is five times more likely to have symptoms of SAD, the Journal of Affective Disorders report in its December issue. Not every person with SAD has the mutation, but those who have the mutation may be predisposed to developing SAD. Of course,  further studies are needed, but understanding the melanopsin mutation may help improve treatments.

via: Science Daily; Image: Flickr

Embryonic stem cell 

A study of twin four year old girls has identified a rogue cell as a culprit in childhood leukemia.

Both twins were found to have the “pre-leukemic” cells in their bone marrow, although, to date, only one has developed leukemia. Researchers found they both have “pre-leukemic stem cells” containing a mutated gene, which forms when the DNA is broken and rejoined at another point. The pre-leukemic cells are transferred from one twin to the other in the womb through their shared blood supply. UK researchers reported in Science that a second genetic mutation is needed for full-blown disease to develop. One twin developed acute lymphoblastic leukemia, possibly developing the second mutation after an infection, when she was two-year’s old - but so far her twin sister, is healthy. 

Leukemia occurs when large numbers of white blood cells take over the bone marrow leaving the body unable to produce enough normal blood cells. Along with lymphoma it accounts for almost half of childhood cancers.

Elaine Warburton

Nature Genetics has published a report by scientists in US and Sweden who have discovered how a variant of the BRCA 1 gene helps breast cancer to grow by knocking out a tumor suppressor gene called PTEN.

The link between BRCA 1 and breast cancer was established 10 years ago but questions have been asked as to why this gene causes breast cancer.

PTEN is a key tumor suppressor gene which is knocked out in breast, brain and prostate cancers. PTEN mutations are second only to p53 as being the most frequently present in all cancers, affecting about 30% of them.

Once a cell loses PTEN it has growth advantages over its neighbours and starts on the road to cancer. PTEN mutations increase the activity of various proteins via the PTEN/P13K pathway to promote tumor growth.

The scientists examined 34 biopsies from females with BRCA 1 mutations and found one third of them the PTEN gene was incomplete, almost missing or had reattached itself to other parts of the chromosome.  50% of BRCA 1 genes have the PTEN mutation.

For further information, please go to http://www.nature.com/ng/journal/vaop/ncurrent/abs/ng.2007.39.html

Elaine Warburton