Cancer susceptibility gene mutations in type I and II endometrial cancer

Beverly Long, Jenna Lilyquist, Amy Weaver, Chunling Hu, Rohan Gnanaolivu, Kun Y. Lee, Steven Hart, Eric Polley, Jamie N Bakkum-Gamez, Fergus J Couch, Sean Christopher Dowdy

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalGynecologic Oncology
DOIs
StateAccepted/In press - Jan 1 2018

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Neoplasm Genes
Endometrial Neoplasms
Mutation
Uterine Neoplasms
Hereditary Nonpolyposis Colorectal Neoplasms
Multiplex Polymerase Chain Reaction
DNA
Gene Frequency
Genes

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

Cancer susceptibility gene mutations in type I and II endometrial cancer. / Long, Beverly; Lilyquist, Jenna; Weaver, Amy; Hu, Chunling; Gnanaolivu, Rohan; Lee, Kun Y.; Hart, Steven; Polley, Eric; Bakkum-Gamez, Jamie N; Couch, Fergus J; Dowdy, Sean Christopher.

In: Gynecologic Oncology, 01.01.2018.

Research output: Contribution to journalArticle

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abstract = "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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AU - Long, Beverly

AU - Lilyquist, Jenna

AU - Weaver, Amy

AU - Hu, Chunling

AU - Gnanaolivu, Rohan

AU - Lee, Kun Y.

AU - Hart, Steven

AU - Polley, Eric

AU - Bakkum-Gamez, Jamie N

AU - Couch, Fergus J

AU - Dowdy, Sean Christopher

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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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