Abstract
Distinguishing primary mucinous ovarian tumors from metastases of non-gynecologic mucinous cancers: Can we leverage next-generation sequencing?
Author
person
Muhammad Danyal Ahsan
Weill Cornell Medicine - Qatar, Doha, Qatar
info_outline
Muhammad Danyal Ahsan, Murtaza Qazi, Ryan M Kahn, Emily M Webster, Sarah R. Levi, Benedict Harvey, Luiza Perez, Jesse T Brewer, Laura Keenahan, Gaurav Thareja, Ravi N. Sharaf, Evelyn Cantillo, Eloise Chapman-Davis, Melissa Kristen Frey, Dennis S Chi, Kevin Holcomb
Full text
Authors
person
Muhammad Danyal Ahsan
Weill Cornell Medicine - Qatar, Doha, Qatar
info_outline
Muhammad Danyal Ahsan, Murtaza Qazi, Ryan M Kahn, Emily M Webster, Sarah R. Levi, Benedict Harvey, Luiza Perez, Jesse T Brewer, Laura Keenahan, Gaurav Thareja, Ravi N. Sharaf, Evelyn Cantillo, Eloise Chapman-Davis, Melissa Kristen Frey, Dennis S Chi, Kevin Holcomb
Organizations
Weill Cornell Medicine - Qatar, Doha, Qatar, Weill Cornell Medicine, New York, NY, Memorial Sloan Kettering Cancer Center, New York, NY
Abstract Disclosures
Research Funding
No funding received
None.
Background:
Primary mucinous ovarian cancers (MOC) are histopathologically challenging to differentiate from ovarian metastases of non-gynecologic origin, with this distinction being critical for appropriate management and prognosis. We compared the somatic gene variant landscape of MOC to that of non-gynecologic mucinous tumors.
Methods:
Data were extracted from the American Association for Cancer Research’s (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) database version 13.0 via cBioPortal. This publicly available, multi-institutional database provides next generation sequencing (NGS) genomic profiles of tumors. We queried this database for samples of MOC, mucinous colorectal cancer (MCRC), mucinous appendiceal cancer (MAC), mucinous breast cancer (MBC) and gastric type mucinous cancer (GMC). Frequencies of somatic gene variants including mutations, copy number alterations and structural variants were compared using Chi-squared or Fischer’s exact tests, using the Benjamini-Hochberg method to control for multiple hypothesis testing with q-values reported.
Results:
A total of 883 tumors were included for analysis: 358 MCRC, 268 MAC, 157 MOC, 59 MBC and 41 GMC samples. Compared to MAC, MOC samples had higher variant frequencies of
CDKN2A
(33.3% vs 0.4%, q<0.001),
CDKN2B
(24.0% vs 0.0%, q<0.001),
TP53
(64.3% vs 23.5%, q<0.001),
ERBB2
(14.3% vs 1.1%, q<0.001) and
CDK12
(13.2% vs 0.0%, q<0.001), whereas
GNAS
variants were more common in MAC (45.5% vs 5.7%, q<0.001). Compared to MCRC, MOC samples had higher variant frequencies of
CDKN2A
(33.3% vs 2.3%, q<0.001),
CDKN2B
(24.0% vs 3.7%, q<0.001),
TP53
(64.3% vs 42.9%, q<0.001),
KRAS
(69.4% vs 51.1%, q<0.001) and
ERBB2
(14.3% vs 5.3%, q<0.001), whereas MCRC had higher variant frequencies of 57 genes, with the largest differentials among
APC
(48.8% vs 2.6%, q<0.001),
SMAD4
(25.2% vs 5.8%, q<0.001) and
TCF7L2
(19.0% vs 0.0%, q<0.001). Samples of MOC had significantly higher rates of
KRAS
variants compared to GMC (69.4% vs 31.7%, q<0.001) and lower rates of
STK11
variants (1.9% vs 22.0%, q<0.001). Compared to MBC, MOC samples had higher variant rates of
CDKN2A
(33.3% vs 3.4%, q<0.001),
TP53
(64.3% vs 10.2%, q<0.001) and
KRAS
(69.4% vs 0.0%, q<0.001), whereas MBC samples had higher variant frequencies of 11 genes, with the largest differentials among
GATA3
(32.1% vs 0.8%, q<0.001),
FGF3
(30.4% vs 2.4%, q<0.05) and
CCND1
(28.1% vs 1.6%, q<0.001).
Conclusions:
NGS demonstrates that MOCs carry a distinct genetic signature compared to mucinous tumors of non-gynecologic origin, most commonly with significantly higher variant frequencies of
CDKN2A
,
CDKN2B
and lower variant frequencies of
GNAS
,
APC
,
STK11
and
GATA3
. This provides rationale for prospective studies evaluating genetic signatures as an adjunct to histopathology in the diagnosis of primary MOC.
7 organizations
15 drugs
2 targets
Organization
Weill Cornell Medicine - QatarOrganization
Doha, QatarOrganization
QatarOrganization
New York Oncology Hematology PCOrganization
Nykode TherapeuticsOrganization
Memorial Sloan Kettering Cancer CenterDrug
CDKN2A/BDrug
CDKN2BDrug
TP53Drug
ERBB2Drug
CDK12Drug
GNASDrug
KRASDrug
APC R1468*Drug
SMAD4Drug
TCF7L2Drug
STK11Drug
GATA3Drug
FGF3Drug
CCND1Target
HER2 (ERBB2)Target
CCND1