Which individuals undergoing BRACAnalysis need
Kristen M. Shannon
, Linda H. Rodgers
, Gayun Chan-Smutko
, Michele Gabree
, Paula D. Ryan
Massachusetts General Hospital, Center for Cancer Risk Assessment, Boston, MA;
Fox Chase Cancer Center,
Philadelphia, PA, USA
Deleterious mutations in BRCA1 and BRCA2 include those identiﬁed by sequencing technology
as well as large genomic rearrangements (LGR). The main testing laboratory in the United
States, Myriad Genetics Laboratory (MGL), has deﬁned criteria for inclusion of LGR testing
(i.e., BRACAnalysis Rearrangement Test, or BARTÔ)whenBRCA1 and BRCA2 testing is
ordered. We were interested in determining how many of our patients with LGR mutations in
BRCA1 and BRCA2 fulﬁlled these MGL criteria. A retrospective chart review was performed
on all individuals who underwent genetic testing at our institution since August 2006. Individuals
who underwent LGR testing were classiﬁed as either having or not having a LGR in BRCA1 or
BRCA2. Each individual’s history was classiﬁed as meeting MGL deﬁned LGR criteria, meeting
criteria using third-degree relatives, or not meeting criteria. A total of 257 BART tests were
ordered at our institution from August 2006 to August 2009. Five individuals (1.9%) had an
LGR mutation. Two LGR were identiﬁed in patients who met MGL deﬁned LGR criteria. One
LGR was identiﬁed in a patient that met MGL deﬁned LGR criteria only when using third-
degree relatives. Two LGR were identiﬁed in individuals who did not meet MGL deﬁned criteria.
LGR are present in individuals who do not have a high pretest probability of carrying a mutation in
BRCA1 or BRCA2. These data suggest that when BRCA1 and BRCA2 genetic testing is per-
formed, testing should always include LGR testing so that the results are the most comprehen-
sive and reliable.
Keywords BRCA1, BRCA2, gene, genetic testing
ª 2011 Elsevier Inc. All rights reserved.
Genetic testing for BRCA1 and BRCA2 mutations can provide
individuals and their families with valuable information about
their risk of developing speciﬁc types of cancer. This infor-
mation can then be used to greatly diminish the likelihood of
developing those speciﬁc types of cancer. For example, when
a woman is found to have a BRCA1 or BRCA2 gene mutation,
she is provided with the option to pursue potentially life-saving
surgeries (i.e., bilateral mastectomy and bilateral salpingo-
oophorectomy) to reduce her risk of developing breast and/
or ovarian cancer (1e3). BRCA1 and BRCA2 testing has been
shown to be cost-effective in individuals with a diagnosis
of cancer (4,5) as well as in women without cancer (6).
Furthermore, the beneﬁts of genetic information are not
limited to the individual who is the ﬁrst within a family to test
positive for a germline mutation in BRCA1 or BRCA2. In
a family with a hereditary predisposition, individuals not
carrying the familial mutation are able to avoid invasive
procedures and heightened screening and also are relieved
of the anxiety associated with carrying the familial mutation
(7,8). Thus, the identiﬁcation of a BRCA1 or BRCA2 mutation
can be critical in the medical management of these families
from both a cost and psychological perspective (9,10).
Deleterious mutations in BRCA1 and BRCA2 include those
identiﬁed by sequencing technology as well as large genomic
rearrangements (LGR) that are found with different technol-
ogies (e.g., multiplex ligation-dependent probe ampliﬁcation).
Most LGR mutations in BRCA1 and BRCA2 are missed when
conventional sequencing technologies are used. BRCA1 and
BRCA2 genetic testing is currently only available in the United
States through one company, Myriad Genetics Laboratories
(MGL), as a result of patent issues surrounding these two
Presented in part at the 2009 International Symposium on
Hereditary Breast and Ovarian Cancer. Montreal, Quebec, Canada.
Received June 16, 2011; received in revised form July 7, 2011;
accepted July 11, 2011.
* Corresponding author.
E-mail address: email@example.com
2210-7762/$ - see front matter ª 2011 Elsevier Inc. All rights reserved.
Cancer Genetics 204 (2011) 416e422