Test for Fetal Abnormalities Finds Maternal Cancer

Neil Osterweil

March 06, 2015

LA JOLLA, California — Eunice Lee had a blood test to check for fetal abnormalities in her high-risk pregnancy, but the results astonished her by suggesting more about her own health than her baby's.

Geneticists using a commercial assay to screen for fetal mutations instead found evidence that the expecting mother was harboring an undetected colon tumor.

"I feel like the luckiest person alive," Dr Lee, a San Francisco-based anesthesiologist, told a rapt audience here at the Future of Genomic Medicine VIII.

Although the fetal assay was not designed to detect cancer, it picked up abnormal genetic signals from circulating tumor DNA that the geneticists determined almost certainly came from Dr Lee. When she was 15 weeks pregnant, she underwent a whole-body MRI scan and a 7 cm tumor in the sigmoid colon was detected.

Dr Lee asked her obstetrician whether it would be possible to delay the surgery until after she had the baby. The answer was, "no, this has to come out today."

"Before I knew it, I was dressed in a hospital gown in the hospital that I work at, getting my IV started," said Dr Lee.

With laparoscopic resection, the surgeons were able to completely remove the tumor. Postsurgical staging showed that it was T3N0M0 colon cancer.

Dr Lee is one of more than 40 women who have undergone fetal screening with MaterniT21 (Sequenom) whose blood showed DNA abnormalities suspicious for incidental cancers or other diseases, said Dirk van den Boom, PhD, chief scientific and strategy officer at Sequenom.

The assay uses DNA sequencing to match samples from circulating cell-free DNA with the chromosomes they came from. The geneticists can then generate a Z-score, a mathematical representation of deviation from the norm that, above or below a prespecified level, can indicate an abnormality in a chromosome of interest.

The abnormalities seen are not diagnostic of cancer, Dr van den Boom explained. They could come from systemic lupus erythematosus, organ transplant rejection, or other causes, but test results in several cases have come back suggestive of various malignancies. To date, Sequenom is not aware of any false-positive results.

New Tests

When results from a fetal assay showed signs suggestive of Hodgkin's lymphoma, investigators from the University of Leuven in Belgium were prompted to create a serum assay that could help detect the diagnostic but elusive Reed–Sternberg cells characteristic of Hodgkin's disease, reported Diana Bianchi, MD, executive director of the Mother Infant Research Institute at Tufts Medical Center in Boston.

"Some of these DNA tests are actually going to identify new ways of following cancer," Dr Bianchi explained.

Dr Lee and her son

Hodgkin's lymphoma has been detected with the assay in three women, one of whom was not diagnosed until 6 months after the test, according Nilesh Dharajiya, MD, laboratory director for Sequenom.

Although the assay is not designed to detect cancer, Dr Lee was tested again after surgery. The results came back normal; none of the gross chromosomal abnormalities evident in the first assay were detectable in the second.

No evidence of recurrence or residual disease has been detected at subsequent follow-ups, Dr Lee reported. She delivered a healthy boy who weighed 6 pounds 11 ounces and measured 19 inches at term.

Dr Lee has disclosed no relevant financial relationships. Dr van den Boom and Dr Dharajiya are employees of Sequenom. Dr Bianchi reports receiving honoraria and research funding from Illumina.

Future of Genomic Medicine (FoGM) VIII. Presented March 5, 2015.


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