Can chimerism explain breast/ovarian cancers in BRCA non-carriers from BRCA-positive families?

Hereditary breast and ovarian cancer syndrome (HBOC) is most frequently caused by mutations in BRCA1 or BRCA2 (in short, BRCA) genes. The incidence of hereditary breast and ovarian cancer in relatives of BRCA mutation carriers who test negative for the familial mutation (non-carriers) may be increas...

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Main Authors: Rachel Mitchell, Lela Buckingham, Melody Cobleigh, Jacob Rotmensch, Kelly Burgess, Lydia Usha
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5901986?pdf=render
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spelling doaj-f43a86f8418e4b51b20ad010845fcd562020-11-25T01:45:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01134e019549710.1371/journal.pone.0195497Can chimerism explain breast/ovarian cancers in BRCA non-carriers from BRCA-positive families?Rachel MitchellLela BuckinghamMelody CobleighJacob RotmenschKelly BurgessLydia UshaHereditary breast and ovarian cancer syndrome (HBOC) is most frequently caused by mutations in BRCA1 or BRCA2 (in short, BRCA) genes. The incidence of hereditary breast and ovarian cancer in relatives of BRCA mutation carriers who test negative for the familial mutation (non-carriers) may be increased. However, the data is controversial, and at this time, these individuals are recommended the same cancer surveillance as general population. One possible explanation for BRCA phenocopies (close relatives of BRCA carriers who have developed cancer consistent with HBOC but tested negative for a familial mutation) is natural chimerism where lack of detectable mutation in blood may not rule out the presence of the mutation in the other tissues. To test this hypothesis, archival tumor tissue from eleven BRCA phenocopies was investigated. DNA from the tumor tissue was analyzed using sequence-specific PCR, capillary electrophoresis, and pyrosequencing. The familial mutations were originally detected in the patients' first-degree relatives by commercial testing. The same testing detected no mutations in the blood of the patients under study. The test methods targeted only the known familial mutation in the tumor tissue. Tumor diagnoses included breast, ovarian, endometrial and primary peritoneal carcinoma. None of the familial mutations were found in the tumor samples tested. These results do not support, but do not completely exclude, the possibility of chimerism in these patients. Further studies with comprehensive sequence analysis in a larger patient group are warranted as a chimeric state would further refine the predictive value of genetic testing to include BRCA phenocopies.http://europepmc.org/articles/PMC5901986?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Rachel Mitchell
Lela Buckingham
Melody Cobleigh
Jacob Rotmensch
Kelly Burgess
Lydia Usha
spellingShingle Rachel Mitchell
Lela Buckingham
Melody Cobleigh
Jacob Rotmensch
Kelly Burgess
Lydia Usha
Can chimerism explain breast/ovarian cancers in BRCA non-carriers from BRCA-positive families?
PLoS ONE
author_facet Rachel Mitchell
Lela Buckingham
Melody Cobleigh
Jacob Rotmensch
Kelly Burgess
Lydia Usha
author_sort Rachel Mitchell
title Can chimerism explain breast/ovarian cancers in BRCA non-carriers from BRCA-positive families?
title_short Can chimerism explain breast/ovarian cancers in BRCA non-carriers from BRCA-positive families?
title_full Can chimerism explain breast/ovarian cancers in BRCA non-carriers from BRCA-positive families?
title_fullStr Can chimerism explain breast/ovarian cancers in BRCA non-carriers from BRCA-positive families?
title_full_unstemmed Can chimerism explain breast/ovarian cancers in BRCA non-carriers from BRCA-positive families?
title_sort can chimerism explain breast/ovarian cancers in brca non-carriers from brca-positive families?
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2018-01-01
description Hereditary breast and ovarian cancer syndrome (HBOC) is most frequently caused by mutations in BRCA1 or BRCA2 (in short, BRCA) genes. The incidence of hereditary breast and ovarian cancer in relatives of BRCA mutation carriers who test negative for the familial mutation (non-carriers) may be increased. However, the data is controversial, and at this time, these individuals are recommended the same cancer surveillance as general population. One possible explanation for BRCA phenocopies (close relatives of BRCA carriers who have developed cancer consistent with HBOC but tested negative for a familial mutation) is natural chimerism where lack of detectable mutation in blood may not rule out the presence of the mutation in the other tissues. To test this hypothesis, archival tumor tissue from eleven BRCA phenocopies was investigated. DNA from the tumor tissue was analyzed using sequence-specific PCR, capillary electrophoresis, and pyrosequencing. The familial mutations were originally detected in the patients' first-degree relatives by commercial testing. The same testing detected no mutations in the blood of the patients under study. The test methods targeted only the known familial mutation in the tumor tissue. Tumor diagnoses included breast, ovarian, endometrial and primary peritoneal carcinoma. None of the familial mutations were found in the tumor samples tested. These results do not support, but do not completely exclude, the possibility of chimerism in these patients. Further studies with comprehensive sequence analysis in a larger patient group are warranted as a chimeric state would further refine the predictive value of genetic testing to include BRCA phenocopies.
url http://europepmc.org/articles/PMC5901986?pdf=render
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