In a research article published in this week’s PLoS Medicine, Ann Killary
(from the University of Texas M. D. Anderson Cancer Center) and colleagues
describe a new gene called DEAR1 that is genetically altered by mutation
and deletion in breast tumors, and that may provide a new breast cancer
prognostic marker.

Each year, more than one million women discover that they have breast
cancer. Although breast cancer is usually diagnosed in women in their 50s
or
60s, some women develop breast cancer much earlier. Cancer in younger
women tends to be more likely to recur or spread, and young women with
breast
cancer have a lower overall survival rate than older women with cancer. It
would therefore be particularly useful to be able to identify those young
women who are specifically at the greatest risk of cancer recurrence, so
that they could be offered intensive surveillance.

In this study, the researchers used a genetic technique termed
“suppression subtractive hybridization” to identify a new gene that is
located on
Chromosome 1 in a region where loss of heterozygosity (a specific type of
genetic alteration) regularly occurs. They called the gene ductal
epithelium-associated RING Chromosome 1, or DEAR1. Further analysis of a
series of 14 samples showed that DEAR1 protein expression was reduced or
lost
in 71% of ductal carcinomas in situ (abnormalities that can develop into
breast cancer). Sequence analysis of 55 primary breast tumors obtained
from
The University of Texas M. D. Anderson Cancer tumor bank also showed that
13% contained genetic alterations in DEAR1.

In addition, Ann Killary and colleagues found that DEAR1 expression was
frequently lost in women with early-onset breast cancer and the loss of
DEAR1
expression correlated with a strong family history of breast cancer and
with a breast cancer subtype that has a poor outcome. At 5-year follow-up
of a
cohort of 123 pre-menopausal women with onset of breast cancer between the
ages of 25 and 49 years, DEAR1-positive expression correlated
significantly
with a 95% local recurrence-free survival.

Although laboratory experiments may not necessarily reflect what happens
in people, the authors say that these findings “indicate that DEAR1
expression is an independent predictor of local recurrence in early-onset
breast cancers and suggest that DEAR1-negative staining on
immunohistochemistry could be an important marker to stratify early-onset
breast cancer patients for increased vigilance in follow-up and adjuvant
therapy.”

In a related expert commentary on the new study, Senthil K. Muthuswamy
from the Ontario Cancer Institute, Toronto, Canada, who was not involved
with
the original study, says “these observations identify DEAR1 as an
excellent predictive biomarker for early onset breast cancers”.

Funding: This research was supported by grants from the Texas Advanced
Research Program, the US Department of Defense, and the US National Cancer
Institute Early Detection Research Network to AMK. STL and DSC were
supported by the US National Cancer Institution training grant (T32
CA09299), STL
by the US National Kidney Foundation, and DSC by the Ladies Auxiliary to
the Veterans of Foreign Wars. The M. D. Anderson core facilities for DNA
sequencing, peptide synthesis, nucleic acid extraction, and histopathology
are supported by a grant from the US National Cancer Institute (NCI
CA-16672). Funding agencies had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.

Competing interests: Three of the authors (Steven T. Lott, Dawn S.
Chandler and Ann McNeill Killary) are co-inventors named in the US Patent
#6,943,245 granted 9/13/2005 and US Patent #7,169,384 granted 1/30/2007 to
the University of Texas M. D. Anderson Cancer Center regarding the novel
gene DEAR1 described herein.

Citation:
“DEAR1 Is a Dominant Regulator of Acinar Morphogenesis and an Independent Predictor of Local Recurrence-Free Survival in Early-Onset Breast Cancer.”
Lott ST, Chen N, Chandler DS, Yang Q, Wang L, et al. (2009)
PLoS Med 6(5): e1000068. doi:10.1371/journal.pmed.1000068

Source
PLoS Medicine

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