Molecular profiling of mesonephric and mesonephric-like carcinomas of cervical, endometrial and ovarian origin
Mesonephric carcinoma is a rare cancer that most often arises within the cervix, and less frequently, in the ovary and endometrium. A retrospective search of our CLIA-certified and CAP-accredited reference molecular laboratory database (Foundation Medicine, Inc.) identified 20 mesonephric or mesonep...
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doaj-084d9ff953d44eab8571217dce0682cc2020-12-19T05:08:12ZengElsevierGynecologic Oncology Reports2352-57892020-11-0134100652Molecular profiling of mesonephric and mesonephric-like carcinomas of cervical, endometrial and ovarian originDouglas I. Lin0Nikunj Shah1Julie Y. Tse2Jonathan K. Killian3Amanda Hemmerich4Claire Edgerly5James Haberberger6Eric A. Severson7Richard S.P. Huang8Shakti H. Ramkissoon9Jo-Anne Vergilio10Jeffrey S. Ross11Julia A. Elvin12Foundation Medicine Inc., Cambridge, MA, United States; Corresponding author.Foundation Medicine Inc., Cambridge, MA, United StatesFoundation Medicine Inc., Cambridge, MA, United StatesFoundation Medicine Inc., Cambridge, MA, United StatesFoundation Medicine Inc., Morrisville, NC, United StatesFoundation Medicine Inc., Morrisville, NC, United StatesFoundation Medicine Inc., Morrisville, NC, United StatesFoundation Medicine Inc., Morrisville, NC, United StatesFoundation Medicine Inc., Morrisville, NC, United StatesFoundation Medicine Inc., Morrisville, NC, United States; Wake Forest Comprehensive Cancer Center and Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC, United StatesFoundation Medicine Inc., Cambridge, MA, United StatesFoundation Medicine Inc., Cambridge, MA, United States; Upstate Medical University, Syracuse, NY, United StatesFoundation Medicine Inc., Cambridge, MA, United StatesMesonephric carcinoma is a rare cancer that most often arises within the cervix, and less frequently, in the ovary and endometrium. A retrospective search of our CLIA-certified and CAP-accredited reference molecular laboratory database (Foundation Medicine, Inc.) identified 20 mesonephric or mesonephric-like, cervical (n = 10), endometrial (n = 5), ovarian (n = 4) or peri-bladder (n = 1) carcinomas that had undergone comprehensive genomic profiling via next generation sequencing. Activating KRAS mutations were present in 90%, 18 of 20 cases, including G12V (n = 7), G12D (n = 6), G12A (n = 3) and G12C (n = 2). Other recurrent alterations were identified in ARID1A (25%), PIK3CA (20%), CTNNB1 (15%), TP53 (10%), MLL2 (10%) and CDKN2A (10%). One KRAS wild-type case had a GATA3 mutation as the sole alteration, while the second KRAS wild-type case had an EGFR exon 20 insertion D770_N771insSVD alteration. All tumors were negative for HPV DNA, microsatellite instability, high tumor mutational burden and homologous recombination deficiency. A circulating tumor DNA (ctDNA) liquid biopsy from peripheral blood, which was performed 6 years after original solid tumor resection in one patient with suspected lung metastasis, revealed concordance of KRAS alteration, gains of chromosomes 1q, 2, 10, 12 and 20, plus new TP53 alterations in the liquid biopsy compared to the original sample. KRAS G12 mutation is major driver of mesonephric and mesonephric-like carcinomas, with less frequent contribution by ARID1A and PIK3CA pathways in tumors of non-cervical origin. ctDNA liquid biopsy may be useful in detecting mutations in recurrent or metastatic patients, who may potentially be eligible for trials against emerging targeted therapies.http://www.sciencedirect.com/science/article/pii/S2352578920301181MesonephricCervicalCarcinomactDNALiquid biopsyKRAS |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Douglas I. Lin Nikunj Shah Julie Y. Tse Jonathan K. Killian Amanda Hemmerich Claire Edgerly James Haberberger Eric A. Severson Richard S.P. Huang Shakti H. Ramkissoon Jo-Anne Vergilio Jeffrey S. Ross Julia A. Elvin |
spellingShingle |
Douglas I. Lin Nikunj Shah Julie Y. Tse Jonathan K. Killian Amanda Hemmerich Claire Edgerly James Haberberger Eric A. Severson Richard S.P. Huang Shakti H. Ramkissoon Jo-Anne Vergilio Jeffrey S. Ross Julia A. Elvin Molecular profiling of mesonephric and mesonephric-like carcinomas of cervical, endometrial and ovarian origin Gynecologic Oncology Reports Mesonephric Cervical Carcinoma ctDNA Liquid biopsy KRAS |
author_facet |
Douglas I. Lin Nikunj Shah Julie Y. Tse Jonathan K. Killian Amanda Hemmerich Claire Edgerly James Haberberger Eric A. Severson Richard S.P. Huang Shakti H. Ramkissoon Jo-Anne Vergilio Jeffrey S. Ross Julia A. Elvin |
author_sort |
Douglas I. Lin |
title |
Molecular profiling of mesonephric and mesonephric-like carcinomas of cervical, endometrial and ovarian origin |
title_short |
Molecular profiling of mesonephric and mesonephric-like carcinomas of cervical, endometrial and ovarian origin |
title_full |
Molecular profiling of mesonephric and mesonephric-like carcinomas of cervical, endometrial and ovarian origin |
title_fullStr |
Molecular profiling of mesonephric and mesonephric-like carcinomas of cervical, endometrial and ovarian origin |
title_full_unstemmed |
Molecular profiling of mesonephric and mesonephric-like carcinomas of cervical, endometrial and ovarian origin |
title_sort |
molecular profiling of mesonephric and mesonephric-like carcinomas of cervical, endometrial and ovarian origin |
publisher |
Elsevier |
series |
Gynecologic Oncology Reports |
issn |
2352-5789 |
publishDate |
2020-11-01 |
description |
Mesonephric carcinoma is a rare cancer that most often arises within the cervix, and less frequently, in the ovary and endometrium. A retrospective search of our CLIA-certified and CAP-accredited reference molecular laboratory database (Foundation Medicine, Inc.) identified 20 mesonephric or mesonephric-like, cervical (n = 10), endometrial (n = 5), ovarian (n = 4) or peri-bladder (n = 1) carcinomas that had undergone comprehensive genomic profiling via next generation sequencing. Activating KRAS mutations were present in 90%, 18 of 20 cases, including G12V (n = 7), G12D (n = 6), G12A (n = 3) and G12C (n = 2). Other recurrent alterations were identified in ARID1A (25%), PIK3CA (20%), CTNNB1 (15%), TP53 (10%), MLL2 (10%) and CDKN2A (10%). One KRAS wild-type case had a GATA3 mutation as the sole alteration, while the second KRAS wild-type case had an EGFR exon 20 insertion D770_N771insSVD alteration. All tumors were negative for HPV DNA, microsatellite instability, high tumor mutational burden and homologous recombination deficiency. A circulating tumor DNA (ctDNA) liquid biopsy from peripheral blood, which was performed 6 years after original solid tumor resection in one patient with suspected lung metastasis, revealed concordance of KRAS alteration, gains of chromosomes 1q, 2, 10, 12 and 20, plus new TP53 alterations in the liquid biopsy compared to the original sample. KRAS G12 mutation is major driver of mesonephric and mesonephric-like carcinomas, with less frequent contribution by ARID1A and PIK3CA pathways in tumors of non-cervical origin. ctDNA liquid biopsy may be useful in detecting mutations in recurrent or metastatic patients, who may potentially be eligible for trials against emerging targeted therapies. |
topic |
Mesonephric Cervical Carcinoma ctDNA Liquid biopsy KRAS |
url |
http://www.sciencedirect.com/science/article/pii/S2352578920301181 |
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