Using genetics to predict CRC outcomes

 

BOSTON – Gastroenterologists and GI surgeons had the opportunity to learn more about “Predicting Clinical Outcomes in CRC with Genetics” at the 2017 AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology.

“The topic is extremely significant for two reasons,” said presenter C. Richard Boland, MD, of the University of California in San Diego. “First, we are now able to test colorectal cancer (CRC) for genetic alternations – allowing us to gauge prognosis and, eventually, target specific therapies to the actual tumor,” he said in an interview in advance of the meeting. “Second, the issue of detecting germline mutations in familial lines of CRC is an important factor in diagnosis.”

The talk provided answers to several important questions. What clinical issues do physicians want to solve in their CRC patients? What kinds of genetic tests are available? What questions do they address? And, is there an opportunity to develop a novel, disruptive technical approach to the somatic genetics of a CRC tumor?

“All cancers are genetic diseases, developing as a consequence of cumulative mutations. Each cancer is different, both in terms of total mutational burden, as well as the specific mutations that ‘drive’ the tumor,” explained Dr. Boland. “We will be able to stop tumor growth by inhibiting the driver mutation, once we know what that driver is. This will allow us to make more accurate prognoses and predict tumor responses to specific therapies. The hard part will be having effective therapies for each driver mutation.”

The presentation began with a discussion of optimizing CRC care using genetics, predictive tests (for defective DNA mismatch repair – dMMR), specific tumor mutations and blood tests (for miRNAs or other noncoding RNAs). It also covered the sensitivity of immunohistochemistry (IHC) for dMMR and potential problems with IHC.

Then it detailed an innovative technical proposal whose elements include developing a next-generation sequencing platform for CRC and performing microsatellite instability and other mutational testing for specific genes as test-guided therapies emerge. The session also provided an overview of germline mutation testing, including a description of genes that cause hereditary CRC, are on Myriad’s myRisk panel, and are included on Ambry’s 8 Test Panels.

“We think about 3% or so of CRCs have a strong genetic basis, but probably a lot more have weaker genetic bases,” said Dr. Boland. “When we find strongly penetrant germline mutations, it permits case finding and preventive intervention in family members. It also tells us a lot about how to care for the index individual, since all of these familial syndromes have a wide range of effects on patients.

“The technology driving this type of patient assessment is rapidly developing, and making it easier to find these mutations” he continued. “But it is also confusing when we find unexpected mutations in people who don’t seem to fit the classic disease descriptions.”

Attendees were taught why genetic test of CRCs can help direct patient care, how the tests can be efficiently done using a new diagnostic platform, and the state of germline testing and its interpretation.

Dr. Boland has given a lecture for Ambry Genetics (a genetics testing company) and may give others in the future.

 

BOSTON – Gastroenterologists and GI surgeons had the opportunity to learn more about “Predicting Clinical Outcomes in CRC with Genetics” at the 2017 AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology.

“The topic is extremely significant for two reasons,” said presenter C. Richard Boland, MD, of the University of California in San Diego. “First, we are now able to test colorectal cancer (CRC) for genetic alternations – allowing us to gauge prognosis and, eventually, target specific therapies to the actual tumor,” he said in an interview in advance of the meeting. “Second, the issue of detecting germline mutations in familial lines of CRC is an important factor in diagnosis.”

The talk provided answers to several important questions. What clinical issues do physicians want to solve in their CRC patients? What kinds of genetic tests are available? What questions do they address? And, is there an opportunity to develop a novel, disruptive technical approach to the somatic genetics of a CRC tumor?

“All cancers are genetic diseases, developing as a consequence of cumulative mutations. Each cancer is different, both in terms of total mutational burden, as well as the specific mutations that ‘drive’ the tumor,” explained Dr. Boland. “We will be able to stop tumor growth by inhibiting the driver mutation, once we know what that driver is. This will allow us to make more accurate prognoses and predict tumor responses to specific therapies. The hard part will be having effective therapies for each driver mutation.”

The presentation began with a discussion of optimizing CRC care using genetics, predictive tests (for defective DNA mismatch repair – dMMR), specific tumor mutations and blood tests (for miRNAs or other noncoding RNAs). It also covered the sensitivity of immunohistochemistry (IHC) for dMMR and potential problems with IHC.

Then it detailed an innovative technical proposal whose elements include developing a next-generation sequencing platform for CRC and performing microsatellite instability and other mutational testing for specific genes as test-guided therapies emerge. The session also provided an overview of germline mutation testing, including a description of genes that cause hereditary CRC, are on Myriad’s myRisk panel, and are included on Ambry’s 8 Test Panels.

“We think about 3% or so of CRCs have a strong genetic basis, but probably a lot more have weaker genetic bases,” said Dr. Boland. “When we find strongly penetrant germline mutations, it permits case finding and preventive intervention in family members. It also tells us a lot about how to care for the index individual, since all of these familial syndromes have a wide range of effects on patients.

“The technology driving this type of patient assessment is rapidly developing, and making it easier to find these mutations” he continued. “But it is also confusing when we find unexpected mutations in people who don’t seem to fit the classic disease descriptions.”

Attendees were taught why genetic test of CRCs can help direct patient care, how the tests can be efficiently done using a new diagnostic platform, and the state of germline testing and its interpretation.

Dr. Boland has given a lecture for Ambry Genetics (a genetics testing company) and may give others in the future.

 

BOSTON – Gastroenterologists and GI surgeons had the opportunity to learn more about “Predicting Clinical Outcomes in CRC with Genetics” at the 2017 AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology.

“The topic is extremely significant for two reasons,” said presenter C. Richard Boland, MD, of the University of California in San Diego. “First, we are now able to test colorectal cancer (CRC) for genetic alternations – allowing us to gauge prognosis and, eventually, target specific therapies to the actual tumor,” he said in an interview in advance of the meeting. “Second, the issue of detecting germline mutations in familial lines of CRC is an important factor in diagnosis.”

The talk provided answers to several important questions. What clinical issues do physicians want to solve in their CRC patients? What kinds of genetic tests are available? What questions do they address? And, is there an opportunity to develop a novel, disruptive technical approach to the somatic genetics of a CRC tumor?

“All cancers are genetic diseases, developing as a consequence of cumulative mutations. Each cancer is different, both in terms of total mutational burden, as well as the specific mutations that ‘drive’ the tumor,” explained Dr. Boland. “We will be able to stop tumor growth by inhibiting the driver mutation, once we know what that driver is. This will allow us to make more accurate prognoses and predict tumor responses to specific therapies. The hard part will be having effective therapies for each driver mutation.”

The presentation began with a discussion of optimizing CRC care using genetics, predictive tests (for defective DNA mismatch repair – dMMR), specific tumor mutations and blood tests (for miRNAs or other noncoding RNAs). It also covered the sensitivity of immunohistochemistry (IHC) for dMMR and potential problems with IHC.

Then it detailed an innovative technical proposal whose elements include developing a next-generation sequencing platform for CRC and performing microsatellite instability and other mutational testing for specific genes as test-guided therapies emerge. The session also provided an overview of germline mutation testing, including a description of genes that cause hereditary CRC, are on Myriad’s myRisk panel, and are included on Ambry’s 8 Test Panels.

“We think about 3% or so of CRCs have a strong genetic basis, but probably a lot more have weaker genetic bases,” said Dr. Boland. “When we find strongly penetrant germline mutations, it permits case finding and preventive intervention in family members. It also tells us a lot about how to care for the index individual, since all of these familial syndromes have a wide range of effects on patients.

“The technology driving this type of patient assessment is rapidly developing, and making it easier to find these mutations” he continued. “But it is also confusing when we find unexpected mutations in people who don’t seem to fit the classic disease descriptions.”

Attendees were taught why genetic test of CRCs can help direct patient care, how the tests can be efficiently done using a new diagnostic platform, and the state of germline testing and its interpretation.

Dr. Boland has given a lecture for Ambry Genetics (a genetics testing company) and may give others in the future.