An array CGH based genomic instability index (G2I) is predictive of clinical outcome in breast cancer and reveals a subset of tumors without lymph node involvement but with poor prognosis
<p>Abstract</p> <p>Background</p> <p>Despite entering complete remission after primary treatment, a substantial proportion of patients with early stage breast cancer will develop metastases. Prediction of such an outcome remains challenging despite the clinical use of s...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2012-11-01
|
| Series: | BMC Medical Genomics |
| Subjects: | |
| Online Access: | http://www.biomedcentral.com/1755-8794/5/54 |
| _version_ | 1818885485640024064 |
|---|---|
| author | Bonnet Françoise Guedj Mickael Jones Natalie Sfar Sana Brouste Véronique Elarouci Nabila Banneau Guillaume Orsetti Béatrice Primois Charlotte de Lara Christine Tunon Debled Marc de Mascarel Isabelle Theillet Charles Sévenet Nicolas de Reynies Aurélien MacGrogan Gaëtan Longy Michel |
| author_facet | Bonnet Françoise Guedj Mickael Jones Natalie Sfar Sana Brouste Véronique Elarouci Nabila Banneau Guillaume Orsetti Béatrice Primois Charlotte de Lara Christine Tunon Debled Marc de Mascarel Isabelle Theillet Charles Sévenet Nicolas de Reynies Aurélien MacGrogan Gaëtan Longy Michel |
| author_sort | Bonnet Françoise |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Despite entering complete remission after primary treatment, a substantial proportion of patients with early stage breast cancer will develop metastases. Prediction of such an outcome remains challenging despite the clinical use of several prognostic parameters. Several reports indicate that genomic instability, as reflected in specific chromosomal aneuploidies and variations in DNA content, influences clinical outcome but no precise definition of this parameter has yet been clearly established.</p> <p>Methods</p> <p>To explore the prognostic value of genomic alterations present in primary tumors, we performed a comparative genomic hybridization study on BAC arrays with a panel of breast carcinomas from 45 patients with metastatic relapse and 95 others, matched for age and axillary node involvement, without any recurrence after at least 11 years of follow-up. Array-CGH data was used to establish a two-parameter index representative of the global level of aneusomy by chromosomal arm, and of the number of breakpoints throughout the genome.</p> <p>Results</p> <p>Application of appropriate thresholds allowed us to distinguish three classes of tumors highly associated with metastatic relapse. This index used with the same thresholds on a published set of tumors confirms its prognostic significance with a hazard ratio of 3.24 [95CI: 1.76-5.96] p = 6.7x10<sup>-5</sup> for the bad prognostic group with respect to the intermediate group. The high prognostic value of this genomic index is related to its ability to individualize a specific group of breast cancers, mainly luminal type and axillary node negative, showing very high genetic instability and poor outcome. Indirect transcriptomic validation was obtained on independent data sets.</p> <p>Conclusion</p> <p>Accurate evaluation of genetic instability in breast cancers by a genomic instability index (G2I) helps individualizing specific tumors with previously unexpected very poor prognosis.</p> |
| first_indexed | 2024-12-19T16:06:12Z |
| format | Article |
| id | doaj.art-b40819640a0448a88843a6d1b1f1f9bd |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-12-19T16:06:12Z |
| publishDate | 2012-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj.art-b40819640a0448a88843a6d1b1f1f9bd2022-12-21T20:14:50ZengBMCBMC Medical Genomics1755-87942012-11-01515410.1186/1755-8794-5-54An array CGH based genomic instability index (G2I) is predictive of clinical outcome in breast cancer and reveals a subset of tumors without lymph node involvement but with poor prognosisBonnet FrançoiseGuedj MickaelJones NatalieSfar SanaBrouste VéroniqueElarouci NabilaBanneau GuillaumeOrsetti BéatricePrimois Charlottede Lara Christine TunonDebled Marcde Mascarel IsabelleTheillet CharlesSévenet Nicolasde Reynies AurélienMacGrogan GaëtanLongy Michel<p>Abstract</p> <p>Background</p> <p>Despite entering complete remission after primary treatment, a substantial proportion of patients with early stage breast cancer will develop metastases. Prediction of such an outcome remains challenging despite the clinical use of several prognostic parameters. Several reports indicate that genomic instability, as reflected in specific chromosomal aneuploidies and variations in DNA content, influences clinical outcome but no precise definition of this parameter has yet been clearly established.</p> <p>Methods</p> <p>To explore the prognostic value of genomic alterations present in primary tumors, we performed a comparative genomic hybridization study on BAC arrays with a panel of breast carcinomas from 45 patients with metastatic relapse and 95 others, matched for age and axillary node involvement, without any recurrence after at least 11 years of follow-up. Array-CGH data was used to establish a two-parameter index representative of the global level of aneusomy by chromosomal arm, and of the number of breakpoints throughout the genome.</p> <p>Results</p> <p>Application of appropriate thresholds allowed us to distinguish three classes of tumors highly associated with metastatic relapse. This index used with the same thresholds on a published set of tumors confirms its prognostic significance with a hazard ratio of 3.24 [95CI: 1.76-5.96] p = 6.7x10<sup>-5</sup> for the bad prognostic group with respect to the intermediate group. The high prognostic value of this genomic index is related to its ability to individualize a specific group of breast cancers, mainly luminal type and axillary node negative, showing very high genetic instability and poor outcome. Indirect transcriptomic validation was obtained on independent data sets.</p> <p>Conclusion</p> <p>Accurate evaluation of genetic instability in breast cancers by a genomic instability index (G2I) helps individualizing specific tumors with previously unexpected very poor prognosis.</p>http://www.biomedcentral.com/1755-8794/5/54Breast cancerArray CGHPrognosisGenetic instability |
| spellingShingle | Bonnet Françoise Guedj Mickael Jones Natalie Sfar Sana Brouste Véronique Elarouci Nabila Banneau Guillaume Orsetti Béatrice Primois Charlotte de Lara Christine Tunon Debled Marc de Mascarel Isabelle Theillet Charles Sévenet Nicolas de Reynies Aurélien MacGrogan Gaëtan Longy Michel An array CGH based genomic instability index (G2I) is predictive of clinical outcome in breast cancer and reveals a subset of tumors without lymph node involvement but with poor prognosis BMC Medical Genomics Breast cancer Array CGH Prognosis Genetic instability |
| title | An array CGH based genomic instability index (G2I) is predictive of clinical outcome in breast cancer and reveals a subset of tumors without lymph node involvement but with poor prognosis |
| title_full | An array CGH based genomic instability index (G2I) is predictive of clinical outcome in breast cancer and reveals a subset of tumors without lymph node involvement but with poor prognosis |
| title_fullStr | An array CGH based genomic instability index (G2I) is predictive of clinical outcome in breast cancer and reveals a subset of tumors without lymph node involvement but with poor prognosis |
| title_full_unstemmed | An array CGH based genomic instability index (G2I) is predictive of clinical outcome in breast cancer and reveals a subset of tumors without lymph node involvement but with poor prognosis |
| title_short | An array CGH based genomic instability index (G2I) is predictive of clinical outcome in breast cancer and reveals a subset of tumors without lymph node involvement but with poor prognosis |
| title_sort | array cgh based genomic instability index g2i is predictive of clinical outcome in breast cancer and reveals a subset of tumors without lymph node involvement but with poor prognosis |
| topic | Breast cancer Array CGH Prognosis Genetic instability |
| url | http://www.biomedcentral.com/1755-8794/5/54 |
| work_keys_str_mv | AT bonnetfrancoise anarraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT guedjmickael anarraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT jonesnatalie anarraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT sfarsana anarraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT brousteveronique anarraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT elaroucinabila anarraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT banneauguillaume anarraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT orsettibeatrice anarraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT primoischarlotte anarraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT delarachristinetunon anarraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT debledmarc anarraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT demascarelisabelle anarraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT theilletcharles anarraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT sevenetnicolas anarraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT dereyniesaurelien anarraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT macgrogangaetan anarraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT longymichel anarraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT bonnetfrancoise arraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT guedjmickael arraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT jonesnatalie arraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT sfarsana arraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT brousteveronique arraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT elaroucinabila arraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT banneauguillaume arraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT orsettibeatrice arraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT primoischarlotte arraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT delarachristinetunon arraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT debledmarc arraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT demascarelisabelle arraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT theilletcharles arraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT sevenetnicolas arraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT dereyniesaurelien arraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT macgrogangaetan arraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis AT longymichel arraycghbasedgenomicinstabilityindexg2iispredictiveofclinicaloutcomeinbreastcancerandrevealsasubsetoftumorswithoutlymphnodeinvolvementbutwithpoorprognosis |