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Non-uniform genetic mutations identified in lung cancers could lead to targeted treatment

Date:
April 23, 2014
Source:
University of Melbourne
Summary:
Three of the more common genetic mutations and their distribution across individual lung cancers have been extensively studied by researchers to see if they matched up to regions of different tumor architecture under the microscope.

The research, published in the journal Oncotarget, explored tumor heterogeneity -- where different cells have different appearances or their own DNA signatures within the same cancer. Such differences could make it difficult to design effective, targeted treatment strategies.

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Firstly they confirmed the mutual exclusivity between the EGFR mutation and either the KRAS or BRAF mutation. Secondly, they found that lung cancers driven by the EGFR gene mutation have that specific mutation present uniformly throughout the tumor, regardless of microscopic appearance. In stark contrast, they discovered that some tumors, with either KRAS or BRAF gene mutations, do not have the mutation present in all parts of the tumor.

Lead researcher Associate Professor Gavin Wright from the University of Melbourne and Director of Surgical Oncology at St Vincent's Hospital, said the findings are good news for patients whose tumors contain treatable mutations in the EGFR gene.

Lung adenocarcinomas (the most common form of lung cancer) that feature the EGFR gene mutation tend to occur in women and non-smokers. They are very effectively treated by the oral drug gefitinib, so it is vital that this mutation is accurately detected.

"Because we found that this particular EGFR mutation was present throughout all areas of such tumors tested, patients with this mutation will be easily identified, even by small needle biopsies."

"This means they will always be offered the appropriate targeted treatment drug, which is more effective than standard chemotherapy for these cases," he said.

"Fortunately, the diagnostic accuracy for biopsies of lung cancers with this mutation is only dependent on there being sufficient tumor cells for testing."

The story is a little more complicated for other lung cancers, though. The researchers found that two less common mutations -- KRAS and BRAF -- could be missed in small biopsy samples. In more than a quarter of the cases they tested, the mutation was only present in one subtype of the tumor and not necessarily uniformly.

"These genetic mutations cannot be so confidently biopsied due to the possibility of being absent in a significant component but present in only the more aggressive part of the cancer," Associate Professor Wright said.

"These findings have significance for diagnostics and for precision medicine in lung adenocarcinoma and may lead to similar studies in other tumor types."


Story Source:

The above story is based on materials provided by University of Melbourne. Note: Materials may be edited for content and length.


Journal Reference:

  1. Gavin Wright et al. Mapping of actionable mutations to histological subtype domains in lung adenocarcinoma: implications for precision medicine. Oncotarget, March 2014 [link]

Cite This Page:

University of Melbourne. "Non-uniform genetic mutations identified in lung cancers could lead to targeted treatment." ScienceDaily. ScienceDaily, 23 April 2014. <www.sciencedaily.com/releases/2014/04/140423101854.htm>.
University of Melbourne. (2014, April 23). Non-uniform genetic mutations identified in lung cancers could lead to targeted treatment. ScienceDaily. Retrieved March 5, 2015 from www.sciencedaily.com/releases/2014/04/140423101854.htm
University of Melbourne. "Non-uniform genetic mutations identified in lung cancers could lead to targeted treatment." ScienceDaily. www.sciencedaily.com/releases/2014/04/140423101854.htm (accessed March 5, 2015).

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