Combination of solid and liquid biopsy genomic profiling for tumor heterogeneity characterization

Background: The potential added value of liquid biopsy (LB) is not well determined in the case of small cell lung cancer (SCLC), an aggressive tumor that can occur either de novo or from the histologic transformation of non-small cell lung cancer (NSCLC). Methods: A systematic review of studies adopting LB in patients with SCLC have been performed to assess the clinical utility of circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs). Results: After a screening of 728 records, 62 studies (32 evaluating CTCs, 27 ctDNA, and 3 both) met predetermined eligibility criteria. Only four studies evaluated LB in the diagnostic setting for SCLC, while its prognostic significance was evaluated in 38 studies and prominently supported by both ctDNA and CTCs. A meta-analysis of 11 studies as for CTCs enumeration showed an HR for overall survival of 2.63 (1.71–4.05), with a potential publication bias. The feasibility of tumor genomic profiling and the predictive role of LB in terms of response/resistance to chemotherapy was assessed in 11 and 24 studies, respectively, with greater consistency for those regarding ctDNA. Intriguingly, several case reports suggest that LB can indirectly capture the transition to SCLC in NSCLC treated with EGFR tyrosine kinase inhibitors. Conclusions: While dedicated trials are needed, LB holds potential clinical roles in both de novo and transformed SCLC. CtDNA analysis appears the most valuable and practicable tool for both disease monitoring and genomic profiling.

Download Full-text

Genomic profiling of mesonephric and mesonephric-like carcinomas via solid and liquid biopsy reveals driver mutations and opportunities for targeted therapies

Gynecologic Oncology ◽

10.1016/j.ygyno.2020.05.314 ◽

2020 ◽

Vol 159 ◽

pp. 198-199

Author(s):

D.I. Lin ◽

J.Y. Tse ◽

S. Ramkissoon ◽

J.S. Ross ◽

J.A. Elvin

Keyword(s):

Targeted Therapies ◽

Liquid Biopsy ◽

Driver Mutations ◽

Genomic Profiling

Download Full-text

Abstract 4819: Differential evolution of tumor heterogeneity in leiomyosarcomas and liposarcomas suggested by genomic profiling

10.1158/1538-7445.am2015-4819 ◽

2015 ◽

Author(s):

Ali Amin-Mansour ◽

Stefano Sioletic ◽

Scott L. Carter ◽

Levi A. Garraway ◽

George D. Demetri ◽

...

Keyword(s):

Differential Evolution ◽

Tumor Heterogeneity ◽

Genomic Profiling

Download Full-text

Abstract A1-18: Attacking the SAGA of tumor heterogeneity: The development of a novel technique to provide spatiotemporal genomic profiling of rare cancer cells

10.1158/1538-7445.transcagen-a1-18 ◽

2015 ◽

Author(s):

Jessica Konen ◽

Adam I. Marcus

Keyword(s):

Cancer Cells ◽

Tumor Heterogeneity ◽

Genomic Profiling ◽

Rare Cancer ◽

Novel Technique

Download Full-text

Correction: Genomic profiling reveals spatial intra-tumor heterogeneity in follicular lymphoma

Leukemia ◽

10.1038/s41375-019-0425-9 ◽

2019 ◽

Vol 33 (6) ◽

pp. 1540-1540

Author(s):

Shamzah Araf ◽

Jun Wang ◽

Koorosh Korfi ◽

Celine Pangault ◽

Eleni Kotsiou ◽

...

Keyword(s):

Follicular Lymphoma ◽

Tumor Heterogeneity ◽

Genomic Profiling

Download Full-text

Integrating comprehensive genomic profiling into the clinical management of prostate cancer patients: A single institution community practice experience.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.281 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 281-281

Author(s):

Neal D. Shore ◽

James Haberberger ◽

Eric Allan Severson ◽

Brian Michael Alexander ◽

Pratheesh Sathyan ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Liquid Biopsy ◽

Clinical Management ◽

Additional Patient ◽

Genomic Profiling ◽

Data Set ◽

Tissue Samples ◽

Comprehensive Genomic Profiling ◽

Germline Testing

281 Background: Prostate cancer is a leading cause of cancer-related mortality with a 5-year survival rate of 69%. In this study, we examine the role of integrating CGP, including tissue and liquid biopsy testing, into the clinical management of prostate cancer patients. Methods: We analyzed 140 cases of advanced prostate carcinoma with tissue and ctDNA based Comprehensive Genomic Profiling (CGP). CGP analysis revealed genomic alterations (GAs), TMB and MSI status. Germline testing, using multiple commercially assays was also obtained. Results: The median age of patients tested by tissue-based and liquid-based CGP was 65 years (46 to 85 yrs) and 69 years (51 to > 89 years), respectively. CGP analysis of tissue samples revealed the most commonly altered genes to be TP53 (34.6%), TMPRSS2- ERG (25.9%), PTEN (23.5%), NBN (14.8%), MYC (13.6%), BRCA2 (14.3%) and CDKN2A (13.3%). TMB analysis determined in 77 tissue samples showed a median (mean) value of 2.61 (5.00) mutations/Mb. 3.9% cases (3/77) were found to be hypermutated. MSI status was determined in 74 cases of which 2.7% (2/74) were found to be MSI-High. Of the tissue-based samples tested, 30.9% (25/81) were derived from metastatic sites. Analysis of commonly altered genes between primary vs metastatic tissue samples revealed TP53 mutations were significantly enriched in metastatic tumors. CGP analysis of the 59 liquid biopsy samples revealed the most commonly altered genes to be TP53 (37.3%), NF1 (10.2%), ATM (10.2%), CHEK2 (8.5%) and GNAS (8.5%). Germline testing was performed as described above on a clinically indicated subset of patients, which revealed alterations in BRCA, ATM, CHEK2, BRIP1 and TP53, among others. We are evaluating additional patient samples as part of the data set, which will be added to the final abstract presentation with a cutoff date of 12-31-2019. Conclusions: Genomic testing for high risk and advanced prostate cancer patients per the NCCN recommendations, with somatic testing, using tissue and liquid biopsy testing, as well as germline testing in selected cases, identifies DNA alterations which have potential clinical utility for clinical trial enrollment.

Download Full-text