TY - JOUR
T1 - Cancer susceptibility gene mutations in type I and II endometrial cancer
AU - Long, Beverly
AU - Lilyquist, Jenna
AU - Weaver, Amy
AU - Hu, Chunling
AU - Gnanaolivu, Rohan
AU - Lee, Kun Y.
AU - Hart, Steven N.
AU - Polley, Eric C.
AU - Bakkum-Gamez, Jamie N.
AU - Couch, Fergus J.
AU - Dowdy, Sean C.
N1 - Funding Information:
Dr. Couch reports funding from the National Institute of Health. The other authors have no conflicts of interest.
Funding Information:
Dr. Couch reports funding from the National Institute of Health . The other authors have no conflicts of interest.
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2019/1
Y1 - 2019/1
N2 - Objectives: To determine the incidence of germline cancer predisposition gene mutations in patients with endometrial cancer (EC) subtypes. Methods: Germline DNA was extracted from whole blood collected from consenting patients undergoing primary surgery for EC between 5/2005 and 11/2016. DNA samples were evaluated by product sequencing from a targeted multiplex PCR panel including 21 known/suspected cancer predisposition genes. Variants were classified as pathogenic/likely pathogenic based on allele frequency (<0.003), effects on protein function, and ClinVar assertions. Results: Germline panel testing was performed on 1170 cases of EC; 849 (72.6%) were type I, and 321 (27.4%) were type II EC, including 135 (11.5%) uterine serous cancers (USC). BRCA1 mutations were enriched in Type II EC compared to Type I EC (0.93% vs. 0.12%, p = 0.07). Lynch Syndrome (LS) mutations were identified in 1.4% of type I and 1.6% of type II EC (p = 0.79), including 1.5% for USC. In total, predisposition gene mutations were present in 4.2% of type I and 5.3% of type II EC, as well as 6.7% of patients with USC). Conclusions: BRCA1/2 and Lynch mutations were rare in this cohort of unselected patients with type I and II EC, including USC. However, the presence of predisposition gene mutations in 4.2% of EC type I, 5.3% of EC type II, and 6.7% of USC suggests that somatic mutation testing should be considered for all EC patients.
AB - Objectives: To determine the incidence of germline cancer predisposition gene mutations in patients with endometrial cancer (EC) subtypes. Methods: Germline DNA was extracted from whole blood collected from consenting patients undergoing primary surgery for EC between 5/2005 and 11/2016. DNA samples were evaluated by product sequencing from a targeted multiplex PCR panel including 21 known/suspected cancer predisposition genes. Variants were classified as pathogenic/likely pathogenic based on allele frequency (<0.003), effects on protein function, and ClinVar assertions. Results: Germline panel testing was performed on 1170 cases of EC; 849 (72.6%) were type I, and 321 (27.4%) were type II EC, including 135 (11.5%) uterine serous cancers (USC). BRCA1 mutations were enriched in Type II EC compared to Type I EC (0.93% vs. 0.12%, p = 0.07). Lynch Syndrome (LS) mutations were identified in 1.4% of type I and 1.6% of type II EC (p = 0.79), including 1.5% for USC. In total, predisposition gene mutations were present in 4.2% of type I and 5.3% of type II EC, as well as 6.7% of patients with USC). Conclusions: BRCA1/2 and Lynch mutations were rare in this cohort of unselected patients with type I and II EC, including USC. However, the presence of predisposition gene mutations in 4.2% of EC type I, 5.3% of EC type II, and 6.7% of USC suggests that somatic mutation testing should be considered for all EC patients.
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U2 - 10.1016/j.ygyno.2018.10.019
DO - 10.1016/j.ygyno.2018.10.019
M3 - Article
C2 - 30612635
AN - SCOPUS:85055535305
SN - 0090-8258
VL - 152
SP - 20
EP - 25
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 1
ER -