Genetic Testing
There are also several limitations associated with genetic testing of germline or inherited mutations , Dr . Godley added . For example , the tissues that are easiest to use in testing for germline mutations – blood and BM – are the tissues affected in hematologic conditions .
“ There is an accumulation of mutations during the development of diseases , so if we test the blood and BM we can ’ t tell if the mutation was acquired with the development of the disease or if it was inherited ,” Dr . Godley explained . “ In hematologic patients , we have to go to extra lengths to test DNA that represents inherited genetic material .”
That additional testing introduces another limitation : time . Skin fibroblasts are effective for detecting germline mutations in patients with hematologic malignancies , she explained , but “ we have to take a skin biopsy and it takes weeks for skin to grow out .” open clinics specifically for this condition . There are still many unanswered questions about the implications of a CHIP diagnosis , including why it progresses to cancer in certain patients and not others and whether there is a way to intervene to prevent malignant transformation .
CHIP has the potential to aid in early detection , change the standard of care for hematologic malignancies , and improve outcomes for patients with myelodysplastic syndromes or acute myeloid leukemia . For now , though , clinicians lack formal guidelines for how to treat a patient when CHIP is identified .
“ As we begin to do deeper sequencing , we can find mutations in everybody at low levels ,” said Ross Levine , MD , director of the Center for Hematologic Malignancies at Memorial Sloan Kettering Cancer Center , which recently launched a specialty CHIP clinic . Dr . Levine also is the vice chair of the ASH Committee on Scientific Affairs and a member of the ASH Task Force on Precision Medicine . “ It ’ s not just whether a patient has these mutations , but also whether he or she has mutations at enough of a burden to be clinically relevant . That ’ s one of the questions the field needs to figure out .”
“In hematologic patients , we have to go to extra lengths to test DNA that represents inherited genetic material .”
— LUCY GODLEY , MD , PhD
“ These patients often need to be transplanted quickly ,” she said . Finding an appropriate donor , which is often a limitation even when germline mutations are not present , becomes a greater obstacle when germline mutations are found .
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A CHIP off the Old Block
In a 2015 Blood article , authors coined the term “ clonal hematopoiesis of indeterminate potential ,” or CHIP , to describe patients who have detectable somatic ( or acquired ) clonal mutations in genes recurrently mutated in hematologic malignancies , but without overt signs of a hematologic malignancy or other clonal disorder . 7
In 2014 , researchers found that CHIP was associated with increased risks of hematologic malignancies , all-cause mortality , and cardiovascular disease – suggesting that clonal hematopoiesis was a precursor to cancer . 8-10 For other patients , though , it was just an innocuous aspect of aging .
The discovery of CHIP sparked interest in this premalignant state and even prompted some cancer centers to
60 ASH Clinical News