Page 91 - Genomic Medicine in Emerging Economies

80 CHAPTER 5: Screening for Hereditary Cancer in Latin America

mutation 5382insC (now c.5266insC) represents 24% of all carrier families
and 11% presented 3450delCAAG (now c.3331_3334delCAAG) (Fernandes
et al., 2016). In Chile, our group has already screened BRCA1 and BRCA2 in
453 patients with breast cancer patients, with or without family history. The
results of this study, in addition to previous ones, led us to define nine founder
mutations in Chilean patients (Alvarez et al., 2017). The most striking find-
ing is that these nine founder mutations are present in 78% of the 71 Chilean
breast cancer carriers detected among the 453 patients. In a collaborative study,
we have demonstrated that mutation 3450delCAAG, which is also founder in
Colombia, has a common Spanish origin that arrived independently in Chile
and Colombia (Tuazon et al., manuscript in preparation). It is worth point-
ing out that, except for the Ashkenazi Jewish mutations and the highly recur-
rent 3450delCAAG in BRCA1, the recurrent mutations found in Latin America
do not overlap between the different countries on the continent. These find-
ings strongly support the idea that a specific panel of recurrent and or founder
mutations must be generated independently in each Latin American country
for the screening of BRCA1 and BRCA2 mutations in breast cancer patients.

Shared Mutations Among Latin American Breast Cancer
Patients
Among their patients, Brazil and Argentina show the highest number of
shared mutations in BRCA1 and BRCA2 (n = 13), followed by Mexico/
Argentina (n = 8), Chile/Argentina (n = 7) and Chile/Brazil (n = 6). The
other countries scarcely share one or two mutations with other Latin
American populations (Colombia, Costa Rica, Peru, Puerto Rico, Uruguay
and Venezuela), or none (Cuba). Observed in more countries is the muta-
tion BRCA2 c.2808_2811delACAA (also described as c.2806_2809delAAAC,
3034del4, or 3036del4), which has been described recurrently in Europe and
is a founder mutation in Colombia (Torres et al., 2007). This mutation is
recurrent in Argentina (Solano et al., 2016), Brazil (Fernandes et al., 2016),
Colombia (Torres et al., 2007) and Peru (Abugattas et al., 2015), reported in
two to eight patients, and observed only once in Venezuela (Lara et al., 2012)
and Mexico (Torres-Mejia et al., 2015). Another mutation observed in several
countries is the Spanish founder mutation c.211A>G (also known as R71G),
found in one patient from Chile (Alvarez et al., 2017) and Mexico (Villarreal-
Garza et al., 2015a), and recurrent in Argentina (n = 11) (Solano et al., 2016)
and in the northeast of Brazil (n = 5) (Felix et al., 2014). Another 31 mutations
are shared only by two or three countries and close to a hundred are not even
shared, so the vast majority of mutations in Latin American patients are not
common.
A different approach for BRCA1 and BRCA2 screening has been carried out
by the group of J. Weitzel who defined a panel of 50 BRCA1 and 46 BRCA2