200 Distinct signatures of genomic copy number variants define subgroups of merkel cell carcinoma tumors

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer. Most MCC tumors contain integrated Merkel cell polyomavirus DNA (virus-positive MCC, VP-MCC) and carry a low somatic mutation burden whereas virus-negative MCC (VN-MCC) possess numerous ultraviolet-signature mutations. In contrast to viral oncogenes and sequence mutations, little is known about genomic structural variants in MCC. To identify copy number variants in commonly altered genes, we analyzed genomic DNA from 31 tumor samples using the Nanostring nCounter copy number cancer panel. Unsupervised clustering revealed three tumor groups with distinct genomic structural variant signatures. The first cluster was characterized by multiple recurrent deletions in genes such as RB1 and WT1. The second cluster contained eight VP-MCC and displayed very few structural variations. The final cluster contained one VP-MCC and four VN-MCC with predominantly genomic amplifications in genes like MDM4, SKP2, and KIT and deletions in TP53. Overall, VN-MCC contained more structure variation than VP-MCC but did not cluster separately from VP-MCC. The observation that most MCC tumors demonstrate a deletion-dominated structural group signature, independent of virus status, suggests a shared pathophysiology among most VP-MCC and VN-MCC tumors.

Download Full-text

Estimation of the Survival of Patients With Lung Squamous Cell Carcinoma Using Genomic Copy Number Aberrations

Clinical Lung Cancer ◽

10.1016/j.cllc.2015.08.005 ◽

2016 ◽

Vol 17 (1) ◽

pp. 68-74.e5

Author(s):

Yan Cao ◽

Yu Liu ◽

Xin Yang ◽

XiangYang Liu ◽

Naijun Han ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Copy Number ◽

Lung Squamous Cell Carcinoma ◽

Copy Number Aberrations ◽

Genomic Copy Number ◽

Genomic Copy

Download Full-text

Examination of genomic copy number alterations in renal cell carcinoma with sarcomatoid features.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.7_suppl.478 ◽

2015 ◽

Vol 33 (7_suppl) ◽

pp. 478-478

Author(s):

Timothy Ito ◽

Jianming Pei ◽

Essel Dulaimi ◽

Craig Menges ◽

Philip Abbosh ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Copy Number ◽

Genetic Alterations ◽

The Other ◽

Copy Number Alterations ◽

Genomic Copy Number ◽

Genomic Copy ◽

Sarcomatoid Differentiation

478 Background: Sarcomatoid differentiation is an uncommon histological finding in renal cell carcinoma (RCC) that may develop from any RCC subtype and is associated with a very poor prognosis. The identification of genetic alterations that drive this aggressive phenotype could aid in the development of more effective targeted therapies. In this study, we aimed to identify unique copy number alterations (CNAs) in patients with sarcomatoid RCC when compared to those with other RCC subtypes. Methods: Genomic copy number analysis was performed using single nucleotide polymorphism (SNP)-based microarrays on tissue extracted from the tumors of 80 patients (9 with sarcomatoid features (sRCC), 39 clear cell (ccRCC), 26 papillary (pRCC) and 6 chromophobe RCC (chRCC)) who underwent renal mass excision between 2010 - 2014. Statistical analysis was performed using Kaplan Meier (KM) survival analysis, t-tests and Fisher exact tests where appropriate. Results: sRCC tumors exhibited significantly higher numbers of CNAs when compared to ccRCC, pRCC and chRCC (mean 20.1 vs. 6.6 vs. 7.0 vs. 6.3, respectively; p <0.0001). The most common copy number losses occurred in chromosome arms 1p, 3p, 9q, 15q, 18q, 21q, and 22q, with losses of 9q (88%), 15q (77%), 18q (66%), and 22 (77%) being unique among sRCC tumors when compared to the other 3 histologies. The most common copy number gains were in chromosome arms 1q, 8q, 17q, and 20p/q, with 1q (55%) and 8q (66%) gains unique when compared to the other 3 histologies. Of the sRCC tumors, 3 arose from ccRCC, 2 from pRCC and 4 from unclassified RCC. sRCC was associated with worse survival compared to ccRCC, pRCC and chRCC on KM analysis (p=0.0006), and higher rates of lymph node positivity (77% vs. 3% vs. 12% vs. 0%, respectively; p<0.0001) and metastases (100% vs. 13% vs. 4% vs. 0%, respectively; p<0.0001) on presentation were observed with sRCC. Conclusions: Sarcomatoid differentiation in RCC is associated with a high rate of chromosomal changes with unique copy number alterations including losses of 9q, 15q, 18q and 22q and gains of 1q and 8q. Identification and validation of candidate driver genes or tumor suppressor loci within these chromosomal regions may help identify targets for future therapies.

Download Full-text