CLINICAL NEWS
“ he analysis provided a
T
good example of how
genome sequencing
can help provide
clarity in a clinically
ambiguous case.”
—DAVID P. STEENSMA, MD
did not yield a diagnosis.
After discovering that the patient’s mother and sister
also had minor hematologic abnormalities, the investigators suspected a genetic cause may be the culprit.
“We performed whole-exome sequencing to try to better understand her disorder and found a dominant negative
mutation in ALAS2, a gene that is closely associated with
X-linked sideroblastic anemia; however, this patient did
not have ring sideroblasts,” says David P. Steensma, MD, a
co-author of the study.
Because only female carriers were found to be affected,
the researchers also wondered whether there may have
been highly skewed X-inactivation toward the mutant
allele; however, they were surprised to learn that the
severity of the anemia phenotype was not associated with
severe X-inactivation skewing. Instead, they found that
cells expressing the mutant ALAS2 allele exhibited an early
block in red blood cell production – leading to perturbed
erythropoiesis in cells expressing the normal allele. This
was most significant in the proband, who had 82 percent
skewing toward the mutant allele.
“In addition to providing an answer for the mechanism
of anemia in this family, the analysis provided a good example of how genome sequencing can help provide clarity
in a clinically ambiguous case,” Dr. Steensma said. ●
Reference
• Sankaran V, Ulirsch J, Tchaikovskii V, et al. X-linked macrocytic dyserythropoietic anemia in females
with an ALAS2 mutation. J Clin Invest. 2015 February 23. [Epub ahead of print]
Do Clinical Trials Underreport Cancer Drug Toxicities?
Clinical trials may be underreporting patient toxicities from cancer drugs – by up
to 75 percent in some cases – according to
a new study that examined the discrepancies between physician-reported toxicities
and reports from patients themselves.
These study results, published recently in
the Journal of Clinical Oncology, support
greater incorporation of patient-reported
outcomes into toxicity reporting in clinical
trials.
“Information available to oncologists
and their patients about symptomatic
toxicities of anticancer treatments is not
based on direct report by prior patients,
but instead on reports made by clinician
assessment in clinical trials,” the study
authors, led by Massimo Di Maio, MD,
explained. “The accurate description of
occurrence and severity of toxicity of anticancer agents is crucial for an informed
evaluation of their risk-benefit ratio.”
With the current study, Dr. Di Maio
and colleagues examined the agreement
(and disagreement) between physicianand patient-reported toxicities from three
separate randomized trials of anticancer
treatment:
• the ELDA (Elderly Breast Cancer—
Docetaxel Adjuvant) study of
patients aged 65–79 years with earlystage breast cancer
• the GECO (Gemcitabine–Coxib) trial
of patients aged <70 years with