CHEK2 variants in the different HC groups
Applying the Bayesian combination of rules by clinical suspicion
subgroups of the HC cohort, CHEK2 LP/P variants were identified
in 1.3% of HBC cases (n=9), in 0.5% HBOC cases (n=1), 1% of the
hereditary non-polyposis colorectal cancer patients (HNPCC, n=3) and in
one patient from the minority cancer group (0.5%), who had two kidney
tumors, pheochromocytoma and prostate cancer.
Among the 10 families with HBC/HBOC, 2 proband females had two variants
in CHEK2 . One female, with BC at 42, was a compound heterozygous
of a whole CHEK2 deletion and variant c.499G>A. The
other patient with bilateral BC at 35 carried two CHEK2 missense
variants (c.433C>T and c.470T>C) in
trans. Both cases were previously reported by our group (Stradella et
al., 2018). In addition, a third proband diagnosed of BC at age 49
carried the CHEK2 c.349A>G and a pathogenic variant
in ERCC3 , so she could be considered a multilocus inherited
neoplasia allele syndrome (MINAS) patient. Interestingly, the three
HNPCC patients with CHEK2 LP/P variants developed CRC at a young
age (22, 25 and 44) and their tumors were MMR proficient.