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Genomic differences between pure ductal carcinoma in situ of the breast and that associated with invasive disease: a calibrated aCGH study.
Clin Cancer Res. 2008 Jul 15; 14(14):4446-54.CC

Abstract

PURPOSE

In the quest for new targets, genomes of ductal carcinoma in situ (DCIS) and infiltrating duct carcinoma (IDC) have been compared previously; however, genomic alterations associated with cancer progression were difficult to identify. We hypothesized that significant events can be detected by comparing lesions with a broader range of behavior: from pure DCIS to IDC associated with lymph node metastasis.

EXPERIMENTAL DESIGN

Array comparative genomic hybridization, calibrated by self-self hybridization tests, was used to study 6 cases of pure DCIS and 17 cases of DCIS paired with IDC where 8 tumors had spread to the local lymph nodes.

RESULTS

Pure DCIS exhibited a marginally higher degree of genomic complexity than DCIS and IDC components of invasive tumors. The latter two showed similarity between tumors and between components of the same tumor with several regions detected preferentially compared with pure DCIS. IDC associated with lymph node metastases showed similarity of genomic profiles as a group. Gain on 17q22-24.2 was associated with higher histologic grade, large IDC size, lymphatic/vascular invasion, and lymph node metastasis (P < 0.05).

CONCLUSIONS

Our findings suggest that DCIS and IDC are associated with specific genomic events. DCIS associated with IDC is genomically similar to the invasive component and therefore may represent either a clone with high invasive potential or invasive cancer spreading through the ducts. Specifically, gain on 17q22-24.2 is a candidate region for further testing as a predictor of invasion when detected in DCIS and predictor of nodal metastasis when detected in DCIS or IDC.

Authors+Show Affiliations

Division of Applied Medical Oncology, Toronto, Ontario, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18628458

Citation

Iakovlev, Vladimir V., et al. "Genomic Differences Between Pure Ductal Carcinoma in Situ of the Breast and That Associated With Invasive Disease: a Calibrated aCGH Study." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 14, no. 14, 2008, pp. 4446-54.
Iakovlev VV, Arneson NC, Wong V, et al. Genomic differences between pure ductal carcinoma in situ of the breast and that associated with invasive disease: a calibrated aCGH study. Clin Cancer Res. 2008;14(14):4446-54.
Iakovlev, V. V., Arneson, N. C., Wong, V., Wang, C., Leung, S., Iakovleva, G., Warren, K., Pintilie, M., & Done, S. J. (2008). Genomic differences between pure ductal carcinoma in situ of the breast and that associated with invasive disease: a calibrated aCGH study. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 14(14), 4446-54. https://doi.org/10.1158/1078-0432.CCR-07-4960
Iakovlev VV, et al. Genomic Differences Between Pure Ductal Carcinoma in Situ of the Breast and That Associated With Invasive Disease: a Calibrated aCGH Study. Clin Cancer Res. 2008 Jul 15;14(14):4446-54. PubMed PMID: 18628458.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genomic differences between pure ductal carcinoma in situ of the breast and that associated with invasive disease: a calibrated aCGH study. AU - Iakovlev,Vladimir V, AU - Arneson,Nona C R, AU - Wong,Vietty, AU - Wang,Chunjie, AU - Leung,Stephanie, AU - Iakovleva,Gaiane, AU - Warren,Keisha, AU - Pintilie,Melania, AU - Done,Susan J, PY - 2008/7/17/pubmed PY - 2008/9/17/medline PY - 2008/7/17/entrez SP - 4446 EP - 54 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin Cancer Res VL - 14 IS - 14 N2 - PURPOSE: In the quest for new targets, genomes of ductal carcinoma in situ (DCIS) and infiltrating duct carcinoma (IDC) have been compared previously; however, genomic alterations associated with cancer progression were difficult to identify. We hypothesized that significant events can be detected by comparing lesions with a broader range of behavior: from pure DCIS to IDC associated with lymph node metastasis. EXPERIMENTAL DESIGN: Array comparative genomic hybridization, calibrated by self-self hybridization tests, was used to study 6 cases of pure DCIS and 17 cases of DCIS paired with IDC where 8 tumors had spread to the local lymph nodes. RESULTS: Pure DCIS exhibited a marginally higher degree of genomic complexity than DCIS and IDC components of invasive tumors. The latter two showed similarity between tumors and between components of the same tumor with several regions detected preferentially compared with pure DCIS. IDC associated with lymph node metastases showed similarity of genomic profiles as a group. Gain on 17q22-24.2 was associated with higher histologic grade, large IDC size, lymphatic/vascular invasion, and lymph node metastasis (P < 0.05). CONCLUSIONS: Our findings suggest that DCIS and IDC are associated with specific genomic events. DCIS associated with IDC is genomically similar to the invasive component and therefore may represent either a clone with high invasive potential or invasive cancer spreading through the ducts. Specifically, gain on 17q22-24.2 is a candidate region for further testing as a predictor of invasion when detected in DCIS and predictor of nodal metastasis when detected in DCIS or IDC. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/18628458/Genomic_differences_between_pure_ductal_carcinoma_in_situ_of_the_breast_and_that_associated_with_invasive_disease:_a_calibrated_aCGH_study_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=18628458 DB - PRIME DP - Unbound Medicine ER -