Scientists pursue novel screening tests for cancer

Antonio Regalado, Nov 18, 2014, The New York Times:

The Hong Kong scientist who invented a simple blood test to show pregnant women if their babies have Down Syndrome is now testing a similar technology for cancer.

Yuk Ming "Dennis" Lo says screening for signs of cancer from a simple blood draw could cost as little as $1,000. The test works by studying DNA released into a person's bloodstream by dying tumour cells.

The idea is to create a cheap screening test that people might get annually at a doctor's office to spot a tumour at its earliest stage, when it's more easily
treated.

“It took 13 years to develop the prenatal tests, but the path was
untrodden,” said Lo, who is based at the Chinese University of Hong Kong. “Cancer will take a shorter time.”

Both Lo and scientists at The Johns Hopkins University recently used a
technique nearly identical to the one used in the prenatal tests to demonstrate that they could scan a person's blood for evidence of genes that are duplicated, missing or rearranged, something that is a hallmark of cancer cells.

But the testing strategy is very expensive. Tumour DNA is often present in tiny quantities if the cancer is at an early stage. It may account for just 0.01 per cent of the DNA fragments in a blood sample.

That means scientists end up decoding 9,999 bits of normal DNA for every stretch of cancer DNA they encounter. The result: Building up a rough snapshot of the
tumour's genome using sequencing machines can cost $10,000 or more.

Lo says he's now developing a different way to measure DNA that could cut the cost of the cancer test by about 90 per cent. The new method looks for changes in methylation — a chemical modification to DNA that controls gene activity.

The genes of cancer cells widely lose their methylation marks, a feature that Lo says can be reliably spotted using less sequencing. Other scientists say Lo's approach is not yet highly accurate and could incorrectly diagnose many healthy people as having cancer.

Victor Velculescu, a genome scientist at Johns Hopkins, says such false positives are a problem for many screening tests.

“Although the approach used by Dr Lo is an excellent application of this technology, it would have the same hurdle to overcome,” he said.

Lo says he is testing his technique in Hong Kong by following 20,000 people at risk for cancer as part of a $4 million study paid for by the Hong Kong government.

Many are infected with hepatitis B, a virus that can cause liver cancer and is carried by about 10 per cent of the Chinese population.

Currently, Hong Kong residents infected with hepatitis B get ultrasound exams, which can also spot tumours fairly early. Lo says he hopes to determine if a DNA blood test is a better option.

“To make these tests something that anyone can have in the doctor's office could be 20 years away, but that day is coming for sure,” said Andre Marziali, chief scientific officer of Boreal Genomics, a startup developing cancer tests.

Lo licensed his patents on pre-natal testing to a California company, Sequenom, which launched a pregnancy test in 2011. He says he hasn't decided how to commercialise the cancer test yet.