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Abstract 2502: Genetic and functional heterogeneity of DCIS as predictors of invasive cancer

Publication ,  Conference
Fortunato, A; Mallo, D; King, L; Hardman, T; Hall, A; Marks, JR; Hwang, SS; Maley, CC
Published in: Cancer Research
August 15, 2020

Genetic diversity both between and within individual tumors constitutes a challenge to personalized cancer medicine. Intra-tumor heterogeneity provides the genetic fuel for natural selection in clonal evolution and cancer progression. Tumors with high levels of genetic heterogeneity are hypothesized to be more likely to demonstrate aggressive behavior and progress to invasion and metastasis.We analyzed the mutational loads from separate areas of pure DCIS and compared this to genetic heterogeneity in DCIS lesions found adjacent to invasive and metastatic cancer. Two spatially distinct areas of DCIS from each case were macro-dissected and the DNA extracted from FFPE samples. To analyze the data, we developed new bioinformatics methods that allowed analysis of small amounts of degraded DNA extracted from FFPE samples across multiple regions. Our bioinformatics pipeline was optimized on a series of 28 independent technical replicates of the same DNA sample sequenced twice, as training tools to find the best filtering parameters.Whole exome sequencing was performed on each of the two geospatially separated samples for each case. Minimum coverage for inclusion in this study was 40X over at least 50% of the exome. We used the ratio of private mutations (only in 1 area) to public (found in both areas) mutations as a measure of intra-tumor heterogeneity.We present an approach to measure clonal heterogeneity using a bulk sequencing strategy applied to geospatially distinct foci of DCIS. We found statistically significant difference between DCIS adjacent to invasive disease and metastatic patients' genetic divergence (t-test, p=0.013). Our findings suggest that genetic and functional heterogeneity may play an important evolutionary role as a driver for invasive progression.Citation Format: Angelo Fortunato, Diego Mallo, Lorraine King, Timothy Hardman, Allison Hall, Jeffrey R. Marks, Shelley Shelley Hwang, Carlo C. Maley. Genetic and functional heterogeneity of DCIS as predictors of invasive cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2502.

Duke Scholars

Published In

Cancer Research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

August 15, 2020

Volume

80

Issue

16_Supplement

Start / End Page

2502 / 2502

Publisher

American Association for Cancer Research (AACR)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis
 

Citation

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Fortunato, A., Mallo, D., King, L., Hardman, T., Hall, A., Marks, J. R., … Maley, C. C. (2020). Abstract 2502: Genetic and functional heterogeneity of DCIS as predictors of invasive cancer. In Cancer Research (Vol. 80, pp. 2502–2502). American Association for Cancer Research (AACR). https://doi.org/10.1158/1538-7445.am2020-2502
Fortunato, Angelo, Diego Mallo, Lorraine King, Timothy Hardman, Allison Hall, Jeffrey R. Marks, Shelley Shelley Hwang, and Carlo C. Maley. “Abstract 2502: Genetic and functional heterogeneity of DCIS as predictors of invasive cancer.” In Cancer Research, 80:2502–2502. American Association for Cancer Research (AACR), 2020. https://doi.org/10.1158/1538-7445.am2020-2502.
Fortunato A, Mallo D, King L, Hardman T, Hall A, Marks JR, et al. Abstract 2502: Genetic and functional heterogeneity of DCIS as predictors of invasive cancer. In: Cancer Research. American Association for Cancer Research (AACR); 2020. p. 2502–2502.
Fortunato, Angelo, et al. “Abstract 2502: Genetic and functional heterogeneity of DCIS as predictors of invasive cancer.” Cancer Research, vol. 80, no. 16_Supplement, American Association for Cancer Research (AACR), 2020, pp. 2502–2502. Crossref, doi:10.1158/1538-7445.am2020-2502.
Fortunato A, Mallo D, King L, Hardman T, Hall A, Marks JR, Hwang SS, Maley CC. Abstract 2502: Genetic and functional heterogeneity of DCIS as predictors of invasive cancer. Cancer Research. American Association for Cancer Research (AACR); 2020. p. 2502–2502.

Published In

Cancer Research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

August 15, 2020

Volume

80

Issue

16_Supplement

Start / End Page

2502 / 2502

Publisher

American Association for Cancer Research (AACR)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis