Edited by Phil B. Fontanarosa, MD, and Catherine D. DeAngelis, MD, MPH
Identification of specific DNA mismatch repair gene mutations in colorectal
cancers may improve clinical management, but current DNA sequencing techniques
do not detect all mutations. Casey and colleagues report results of a study
comparing conversion analysis vs DNA sequencing to detect 3 mismatch repair
mutations in colorectal cancers. The authors found that conversion analysis
detected more deleterious mutations than conventional DNA sequencing.
Urine cytology is one test used in the diagnosis of bladder cancer,
but it has low sensitivity. Grossman and colleagues investigated whether a
proteomic assay for a tumor marker, nuclear matrix protein NMP22, in voided
urine and available at point-of-care, could improve detection of malignancy
in patients with risk factors or symptoms of bladder cancer. The authors found
that the NMP22 assay to have positive results in 44 of 79 patients with confirmed
bladder cancer, including 4 tumors not seen on cystoscopy, whereas urine cytology
had positive results in only 12 of 76 patients.
Patients infected with human immunodeficiency virus type 1 (HIV-1) who
achieve virus suppression while receiving highly active antiretroviral therapy
(HAART) are known to experience intermittent episodes of detectable viremia
(“blips”). Nettles and colleagues tested the hypothesis that these
blips are random and clinically insignificant by assessing HIV-1 RNA levels
every 2 to 3 days over 3 to 4 months in 10 patients. They found blips in 9
of 10 patients, results that were statistically consistent with random assay
variation and were not associated with concurrent clinical factors, antiretroviral
drug concentrations, or drug resistance mutations.
Recent trials of multidonor islet transplantation for type 1 diabetes
have demonstrated success, but single-donor transplants would be preferable
by allowing more patients access to this treatment and reducing risk. Hering
and colleagues investigated single-donor islet transplant with initiation
of immunosuppression prior to transplantation in all 8 study patients. There
were no serious transplant- or immunosuppression-related adverse events, and
5 of the patients remained insulin-independent at 1 year of follow-up.
Monitoring fetal development is currently limited to noninvasive methods.
Larrabee and colleagues hypothesized that if fetal messenger RNA (mRNA) could
be detected in amniotic fluid, it could be analyzed to study fetal gene expression,
which could reflect fetal well-being. They describe the extraction of fetal
mRNA from cell-free amniotic fluid samples, amplification of the mRNA, and
analysis using gene expression microarrays. Among their findings were gene
expression changes related to sex, gestational age, and disease status.
Monogenic disorders such as β-thalassemia frequently involve single
nucleotide exchange or point mutations, which are challenging to detect using
current techniques. In previous work, Li and colleagues determined that circulatory
fetal DNA can be reliably separated from maternal DNA in samples of maternal
plasma using a size-fractionation technique. In this issue of JAMA, they report successful application of the size-fractionation
technique to detect paternally inherited β-thalassemia point mutations.
Researchers are tackling big projects aimed at improving human health,
including an effort to develop cancer biomarkers and a venture to use microbial
“factories” to supply a key antimalaria drug to developing countries.
Conflicts in defining ownership and control of intellectual contributions
to biomedical discoveries.
Advances in molecular imaging techniques and agents.
The use and future of robotic surgery.
For your patients: Information about bladder cancer.
This Week in JAMA . JAMA. 2005;293(7):771. doi:10.1001/jama.293.7.771