‘Cell of origin’ provides clues for early detection of lung cancer

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Lung CancerScientists at the Walter and Eliza Hall Institute in Melbourne have discovered the cells that are thought to give rise to lung squamous cell carcinoma, the second most common subtype of lung cancer and a disease which primarily affects smokers and ex-smokers.

The study, led by Dr Marie-Liesse Asselin-Labat and PhD student Ms Clare Weeden, used donated lung tissue obtained through the Victorian Cancer Biobank to investigate lung stem cells, with the aim of understanding how cancer could form.

The team isolated cells found in the airway of the lung, called basal stem cells, and discovered that when exposed to harmful chemicals such as cigarette smoke, the cells would try to repair any damage. However, there was a problem: this rapid repair process was riddled with errors.

Dr Asselin-Labat said the team found that despite attempts to help the body repair from damage, the basal stem cell DNA repair process was faulty.

“Our team has unearthed some of the first evidence that the basal stem cell DNA repair process is flawed, pointing to the accumulation of DNA errors and genetic mutations that could eventually lead to cancer,” Dr Asselin-Labat said.

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Further genetic analysis using a technique developed by Professor Gordon Smyth and Dr Yunshun Chen, in the Institute’s bioinformatics department, confirmed a correlation between the genetic signatures of the lung-based basal stem cells and lung squamous cell carcinoma. This genetic data reinforces that lung basal stem cells could be the ‘seed’ from which a cancer is able to ‘grow’.

Ms Weeden said lung cancer was the number one cause of cancer death in the world, with thirty per cent of cases linked to lung squamous cell carcinoma.

“Lung squamous cell carcinoma is a devastating disease with a poor prognosis because the tumours are often discovered too late, when the cancer is inoperable. Therefore, the ability to detect this cancer early would be a real game-changer,” Ms Weeden said.

“The hope going forward, is that our work will be a gateway to new, tailored prevention and treatment measures for patients with lung diseases,” Ms Weeden said.

Despite being the leading cause of cancer death, lung cancer research currently receives about 5% of cancer research funding in Australia.

The researchers wish to acknowledge the following supporters of this vital research: National Health and Medical Research Council of AustraliaVictorian Cancer Biobank, the Royal Melbourne HospitalThe Viertel Charitable Foundation, the Harry Secomb Foundation, the Australian Postgraduate AwardCancer Therapeutics CRC, the Victorian Cancer Agency and the Victorian Government.

The research findings were published in the journal PLOS Biology.
[hr] Source: WEHI


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