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Comprehensive genomic profiling of relapsed and metastatic adenoid cystic carcinomas by next-generation sequencing reveals potential new routes to targeted therapies.

Publication ,  Journal Article
Ross, JS; Wang, K; Rand, JV; Sheehan, CE; Jennings, TA; Al-Rohil, RN; Otto, GA; Curran, JC; Palmer, G; Downing, SR; Yelensky, R; Lipson, D ...
Published in: The American journal of surgical pathology
February 2014

We hypothesized that next-generation sequencing could reveal actionable genomic alterations (GAs) and potentially expand treatment options for patients with advanced adenoid cystic carcinoma (ACC). Genomic profiling using next-generation sequencing was performed on hybridization-captured, adapter ligation libraries derived from 28 relapsed and metastatic formalin-fixed paraffin-embedded ACC. The 3230 exons of 182 cancer-related genes and 37 introns of 14 genes frequently rearranged in cancer were fully sequenced using the Illumina HiSeq 2000. All classes of GAs were evaluated. Actionable GAs were defined as those impacting targeted anticancer therapies on the market or in registered clinical trials. A total of 44 GAs were identified in the 28 ACC tumors, with 12 of 28 (42.9%) of tumors harboring at least 1 potentially actionable GA. The most common nonactionable GAs were identified in KD6MA (5 cases; 18%), ARID1A (4 cases; 14%), RUNX1 (2 cases; 7%), and MYC (2 cases; 7%). Actionable GAs included NOTCH1 (3 cases; 11%), MDM2 (2 cases; 7%), PDGFRA (2 cases; 7%), and CDKN2A/B (p16) (2 cases; 7%). Other potentially actionable GAs identified in a single case included: mutations in AKT1, BAP1, EGFR, and PIK3CA, homozygous deletion of FBXW7, and amplifications of CDK4, FGFR1, IGF1R, KDR, KIT, and MCL1. The frequency of GA in ACC is lower than that seen in the more common solid tumors. Comprehensive genomic profiling of ACC can identify actionable GAs in a subset of patients that could influence therapy for these difficult-to-treat progressive neoplasms.

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Published In

The American journal of surgical pathology

DOI

EISSN

1532-0979

ISSN

0147-5185

Publication Date

February 2014

Volume

38

Issue

2

Start / End Page

235 / 238

Related Subject Headings

  • Tissue Fixation
  • Prognosis
  • Predictive Value of Tests
  • Precision Medicine
  • Phenotype
  • Patient Selection
  • Pathology
  • Paraffin Embedding
  • Neoplasm Recurrence, Local
  • Molecular Targeted Therapy
 

Citation

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Ross, J. S., Wang, K., Rand, J. V., Sheehan, C. E., Jennings, T. A., Al-Rohil, R. N., … Stephens, P. J. (2014). Comprehensive genomic profiling of relapsed and metastatic adenoid cystic carcinomas by next-generation sequencing reveals potential new routes to targeted therapies. The American Journal of Surgical Pathology, 38(2), 235–238. https://doi.org/10.1097/pas.0000000000000102
Ross, Jeffrey S., Kai Wang, Janna V. Rand, Christine E. Sheehan, Timothy A. Jennings, Rami N. Al-Rohil, Geoff A. Otto, et al. “Comprehensive genomic profiling of relapsed and metastatic adenoid cystic carcinomas by next-generation sequencing reveals potential new routes to targeted therapies.The American Journal of Surgical Pathology 38, no. 2 (February 2014): 235–38. https://doi.org/10.1097/pas.0000000000000102.
Ross JS, Wang K, Rand JV, Sheehan CE, Jennings TA, Al-Rohil RN, et al. Comprehensive genomic profiling of relapsed and metastatic adenoid cystic carcinomas by next-generation sequencing reveals potential new routes to targeted therapies. The American journal of surgical pathology. 2014 Feb;38(2):235–8.
Ross, Jeffrey S., et al. “Comprehensive genomic profiling of relapsed and metastatic adenoid cystic carcinomas by next-generation sequencing reveals potential new routes to targeted therapies.The American Journal of Surgical Pathology, vol. 38, no. 2, Feb. 2014, pp. 235–38. Epmc, doi:10.1097/pas.0000000000000102.
Ross JS, Wang K, Rand JV, Sheehan CE, Jennings TA, Al-Rohil RN, Otto GA, Curran JC, Palmer G, Downing SR, Yelensky R, Lipson D, Balasubramanian S, Garcia L, Mahoney K, Ali SM, Miller VA, Stephens PJ. Comprehensive genomic profiling of relapsed and metastatic adenoid cystic carcinomas by next-generation sequencing reveals potential new routes to targeted therapies. The American journal of surgical pathology. 2014 Feb;38(2):235–238.

Published In

The American journal of surgical pathology

DOI

EISSN

1532-0979

ISSN

0147-5185

Publication Date

February 2014

Volume

38

Issue

2

Start / End Page

235 / 238

Related Subject Headings

  • Tissue Fixation
  • Prognosis
  • Predictive Value of Tests
  • Precision Medicine
  • Phenotype
  • Patient Selection
  • Pathology
  • Paraffin Embedding
  • Neoplasm Recurrence, Local
  • Molecular Targeted Therapy