TY - JOUR
T1 - The spectrum of MAPK-ERK pathway genomic alterations in gynecologic malignancies
T2 - Opportunities for novel therapeutic approaches
AU - Nasioudis, Dimitrios
AU - Fernandez, Marta Llaurado
AU - Wong, Nelson
AU - Powell, Daniel J.
AU - Mills, Gordon B.
AU - Westin, Shannon
AU - Fader, Amanda N.
AU - Carey, Mark S.
AU - Simpkins, Fiona
N1 - Publisher Copyright:
© 2023
PY - 2023/10
Y1 - 2023/10
N2 - Objective: To investigate the incidence of MAPK/ERK pathway genomic alterations among patients with gynecologic malignancies. Methods: We accessed the American Association of Cancer Research Genomics Evidence of Neoplasia Information Exchange publicly available dataset (v13.0). Patients with malignant tumors of the ovary, uterus, and cervix were identified. Following stratification by tumor site and histology, we examined the prevalence of MAPK/ERK pathway gene alterations (somatic mutation, and/or structural chromosome alterations). We included the following RAS-MAPK pathway genes known to be implicated in the dysregulation of the pathway; KRAS, NRAS, BRAF, HRAS, MAP2K1, RAF1, PTPN11, NF1, and ARAF. Data from the OncoKB database, as provided by cBioPortal, were utilized to determine pathogenic gene alterations. Results: We identified a total of 10,233 patients with gynecologic malignancies; 48.2% (n = 4937) with ovarian, 45.2% (n = 4621) with uterine and 6.6% (n = 675) with cervical cancer respectively. The overall incidence of MAPK pathway gene alterations was 21%; the most commonly altered gene was KRAS (13%), followed by NF1 (7%), NRAS (1.3%), and BRAF (1.2%). The highest incidence was observed among patients with mucinous ovarian (71%), low-grade serous ovarian (48%), endometrioid ovarian (37%), and endometrioid endometrial carcinoma (34%). Conclusions: Approximately 1 in 5 patients with a gynecologic tumor harbor a MAPK/ERK pathway genomic alteration. Novel treatment strategies capitalizing on these alterations are warranted.
AB - Objective: To investigate the incidence of MAPK/ERK pathway genomic alterations among patients with gynecologic malignancies. Methods: We accessed the American Association of Cancer Research Genomics Evidence of Neoplasia Information Exchange publicly available dataset (v13.0). Patients with malignant tumors of the ovary, uterus, and cervix were identified. Following stratification by tumor site and histology, we examined the prevalence of MAPK/ERK pathway gene alterations (somatic mutation, and/or structural chromosome alterations). We included the following RAS-MAPK pathway genes known to be implicated in the dysregulation of the pathway; KRAS, NRAS, BRAF, HRAS, MAP2K1, RAF1, PTPN11, NF1, and ARAF. Data from the OncoKB database, as provided by cBioPortal, were utilized to determine pathogenic gene alterations. Results: We identified a total of 10,233 patients with gynecologic malignancies; 48.2% (n = 4937) with ovarian, 45.2% (n = 4621) with uterine and 6.6% (n = 675) with cervical cancer respectively. The overall incidence of MAPK pathway gene alterations was 21%; the most commonly altered gene was KRAS (13%), followed by NF1 (7%), NRAS (1.3%), and BRAF (1.2%). The highest incidence was observed among patients with mucinous ovarian (71%), low-grade serous ovarian (48%), endometrioid ovarian (37%), and endometrioid endometrial carcinoma (34%). Conclusions: Approximately 1 in 5 patients with a gynecologic tumor harbor a MAPK/ERK pathway genomic alteration. Novel treatment strategies capitalizing on these alterations are warranted.
KW - Genomics
KW - Ovarian cancer
KW - Therapeutics
KW - Uterine cancer
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U2 - 10.1016/j.ygyno.2023.08.007
DO - 10.1016/j.ygyno.2023.08.007
M3 - Article
C2 - 37657193
AN - SCOPUS:85169816237
SN - 0090-8258
VL - 177
SP - 86
EP - 94
JO - Gynecologic oncology
JF - Gynecologic oncology
ER -