Comprehensive genomic profiling of ctDNA in patients with colon cancer and its fidelity to the genomics of the tumor biopsy.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 569-569 ◽  
Author(s):  
Jeffrey P. Gregg ◽  
Gerald Li ◽  
Dean Pavlick ◽  
Jon Chung ◽  
Matthew Cooke ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Stage Iv ◽  
Prospective Clinical Study ◽  
Genomic Profiling ◽  
Blood Draw ◽  
Tumor Biopsy ◽  
Comprehensive Genomic Profiling ◽  
Tumor Types ◽  
Ct Dna ◽  
Clinical Trial Information

569 Background: The liquid biopsy offers the ability to non-invasively analyze the genome of a tumor through circulating tumor (ct) DNA to identify targetable and prognostic genomic alterations. Few studies have rigorously analyzed ctDNA results and determined the fidelity with which they recapitulate the genomics of the tumor. The clinical utility study (CUS) for FoundationACT (Foundation Medicine, Cambridge, MA; NCT02620527) is a large multi-center prospective clinical study to validate this ctDNA assay for multiple solid tumor types. In this subset of the CUS study, paired specimens from 98 patients with colon cancer were analyzed with comprehensive genomic profiling of the tumor (FoundationOne) and a blood sample (FoundationACT). Methods: Maximum somatic allele fraction (MSAF) was used to estimate the fraction of ctDNA in the sample. The set of genes and targeted regions common to both FoundationOne and FoundationACT were compared for each subject. Results: 60% were male; 73 had stage IV, 17 had stage III, and 8 had stage II disease. 16% of cases had an MSAF value of 0, indicating that no ctDNA were in these samples. For the cases with MSAF > 0, 153 insertion/deletions (indels)/substitutions were identified in the tumor, and 73% of these identical alterations were also identified in the ctDNA samples. As robust analytical performance for FoundationACT has been demonstrated at MSAF > 0.5% for indel/subs, further analysis was conducted using this threshold. 83% of the alterations identified with FoundationOne were identified with FoundationACT. Further, 90% of NRAS/KRAS and 75% BRAF alterations (NCCN guideline genes) were concordant between the two assays. Lastly, there were 11 patients with tumor biopsy and blood draw taken within 30 days of each other, and in these there was 100% concordant. Association of the genomics results with other clinical variables will be presented for the available subset of patients. Conclusions: In cases where tumor profiling is not possible, these results provide compelling evidence that comprehensive molecular profiling of ctDNA in colon cancer can be used to identify most clinically relevant alterations and has fidelity to the genomics of the tumor. Clinical trial information: NCT02620527.

Comprehensive genomic profiling of neuroendocrine carcinoma of the prostate.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 187-187
Author(s):  
Sumanta K. Pal ◽  
Matthew I. Milowsky ◽  
Julia Andrea Elvin ◽  
Siraj Mahamed Ali ◽  
Jean H. Hoffman-Censits ◽  
...  
Keyword(s):  
Neuroendocrine Carcinoma ◽  
Stage Iv ◽  
Mtor Inhibitors ◽  
Mtor Pathway ◽  
Tumor Type ◽  
Genomic Profiling ◽  
Genomic Alterations ◽  
Carcinoma Of The Prostate ◽  
Comprehensive Genomic Profiling ◽  
Metastatic Sites

187 Background: Neuroendocrine carcinoma of the prostate (NCAP) is an aggressive high grade malignancy that often presents as metastatic disease. Current treatments of this tumor have only modest benefit leading investigators to query whether comprehensive genomic profiling (CGP) would have potential to discover novel targets of therapy. Methods: DNA was extracted from 40 microns of FFPE sections from 37 consecutive cases of relapsed/metastatic NCAP. CGP was performed on hybridization-captured, adaptor ligation based libraries to a mean coverage depth of 583X for up to 315 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer. Genomic alterations (GA) included base substitutions (SUB), INDELs, copy number alterations (CNA) and fusions/rearrangements. Clinically relevant GA (CRGA) were defined as GA linked to drugs on the market or under evaluation in mechanism driven clinical trials. Results: The median age of the men in this study was 65.1 years (range 43 to 83 years). All (100%) cases were positive for neuroendocrine markers on immunohistochemical staining and were Stage IV at the time of CGP. Samples used for sequencing were obtained from the primary tumor in 9 (24%) of NCAP and from metastatic sites in 28 (76%) of NCAP (12 liver, 6 LN, 2 each from bladder, pelvis and soft tissue, and 1 each from rectum, bone, urethra and ureter. There were 213 total GA (5.8 GA/sample) and 47 CRGA (1.3 CRGA/sample). The most frequent GA were non-CRGA mutations in TP53 (68%) and RB1 (51%). TMPRSS:ERG fusions were identified in 32% of cases whereas AR was altered in 8% (1 mutation and 2 amplifications). The most frequent CRGA involved PTEN (32%), BRCA2 (14%), FGFR1 (5%), PIK3CA (5%) and AKT2 (3%). No alterations in BRAF were identified. Clinical responses to MTOR inhibitors in patients with MTOR pathway alterations will be presented. Conclusions: NCAP has distinctive genomic alterations from classic acinar CAP including reduced frequencies of alterations in TMPRSS:ERG and AR and frequent RB1 mutations. Multiple alterations in the MTOR pathway identified in this infrequent tumor type suggest that these patients may be candidates for MTOR inhibitors and other targeted therapies.

FoundationOne as a relevant tool for comprehensive genomic profiling and assessment of tumor mutation burden in the era of precision oncology in India.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23096-e23096
Author(s):  
Amit Verma ◽  
Nitesh Rohatgi ◽  
Pramod Kumar Julka ◽  
Meenu Walia ◽  
Ankur Bahl ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Mutation Frequency ◽  
Unknown Primary ◽  
Precision Oncology ◽  
Tumor Type ◽  
Genomic Profiling ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Comprehensive Genomic Profiling ◽  
Tumor Types

e23096 Background: Comprehensive genomic profiling (CGP) is gaining acceptability globally, but clinical experience in developing countries like India is limited. CGP identifies genomic alterations (GA), with tumor mutation burden (TMB) and microsatellite status (MSI), revealing therapeutic options such as targeted inhibitors and immunotherapies. We sought to evaluate the mutation frequency and actionability across tumors. Methods: Metastatic and/or refractory patients (referred to Personalized Cancer Medicine Clinic) underwent CGP analysis, including calculation of TMB and MSI, using a targeted NGS panel (FoundationOne, 53 samples; FoundationOne Heme, 4 samples). This panel detects all relevant classes of GA: base substitutions, small indels, rearrangements and copy number changes. Mutation frequencies were compared with the larger Foundation database. TMB status was reported as low (≤5 mutations/Mb), intermediate (6-19 mut/Mb) or high (≥20 mut/Mb). Results: The most common tumor types were lung (23%), breast (14%) and sarcoma (12%); other tumor types, including unknown primary constituted the rest (51%). Most samples were from metastatic sites (60%). Oncogenic GA were found in 131 genes across all tumor subtypes and affected major pathways: apoptosis/cell cycle (31%), PI3K (14%), transcriptional regulation (13%), and receptor tyrosine kinases (10%). Among these GA, 38 were considered actionable and were distributed across 43 (75%) samples. Therapies with FDA approval for the tumor type analyzed were indicated for 18 samples; an additional 25 samples had GA associated with therapies FDA approved for another indication. More than 1 actionable GA was identified in 24/43 (56%). TMB status was low in 36 (63%), intermediate in 19 (33%) and high in 2 (3.5%). High TMB status correlated with high MSI status (p < 0.001). Trend observed in the mutation frequency was comparable with the larger Foundation database. Conclusions: This is the first study in India showing CGP identified actionable targets associated with FDA approved therapies in approx. 32% of cases. TMB status identified 2/57 samples with high mutation burden for whom immunotherapy might be relevant.

Comprehensive genomic profiling to identify tumor mutational burden (TMB) as an independent predictor of response to immunotherapy in diverse cancers.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14508-e14508 ◽  
Author(s):  
Aaron Goodman ◽  
Shumei Kato ◽  
Lyudmila Bazhenova ◽  
Sandip Pravin Patel ◽  
Garrett Michael Frampton ◽  
...  
Keyword(s):  
Strong Dependence ◽  
Multivariable Analysis ◽  
Favorable Outcome ◽  
Genomic Profiling ◽  
Outcome Parameters ◽  
Patients With Cancer ◽  
Comprehensive Genomic Profiling ◽  
Response Biomarker ◽  
Tumor Mutational Burden ◽  
Tumor Types

e14508 Background: Immunotherapy induces durable responses in a subset of patients with cancer. High TMB may be a response biomarker for PD-1/PD-L1 blockade in tumors such as melanoma and non-small cell lung cancer (NSCLC). Our aim was to examine the relationship between TMB and outcome in diverse cancers treated with various immunotherapies. Methods: We reviewed data on 1,638 patients who had undergone comprehensive genomic profiling and had TMB assessment. Immunotherapy-treated patients (N = 151) were analyzed for response rate (RR), progression-free and overall survival (PFS, OS). Results: Higher TMB was independently associated with better outcome parameters (multivariable analysis). The RR for patients with high (≥ 20 mutations/mb) vs. low to intermediate TMB was 22/38 (58%) vs. 23/113 (20%) (P = 0.0001); median PFS, 12.8 vs. 3.3 months (P = <0.0001); median OS, not reached vs. 16.3 months (P = 0.0036) (Table). Results were similar when anti-PD-1/PD-L1 monotherapy was analyzed (N = 102 patients), with a linear correlation between higher TMB and favorable outcome parameters; the median TMB for responders vs. non-responders treated with anti-PD-1/PD-L1 monotherapy was 18.0 vs. 5.0 mutations/mb (P < 0.0001). Comparable data was observed when patients with melanoma (N = 52) and NSCLC (N = 36) were excluded (N = 63 patients; 19 tumor types). Interestingly, anti-CTLA4/anti-PD-1 combinations vs. anti-PD-1/PD-L1 monotherapy was selected as a factor independent of TMB for predicting better RR (77% vs. 21%) (P = 0.004) and PFS (P = 0.024). Conclusions: Higher TMB predicts favorable outcome to PD-1/PD-L1 blockade across diverse tumors. Benefit from dual checkpoint blockade did not show a similarly strong dependence on TMB. [Table: see text]

Adenocarcinoma (ACB), urothelial carcinoma (UCB) and squamous cell carcinoma (SCCB) of the bladder: A Comprehensive Genomic Profiling (CGP) Study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4533-4533 ◽  
Author(s):  
Joseph Jacob ◽  
Gennady Bratslavsky ◽  
Oleg Shapiro ◽  
Nick Liu ◽  
Elizabeth Kate Ferry ◽  
...  
Keyword(s):  
High Status ◽  
Genomic Profiling ◽  
Dna Repair Genes ◽  
Genomic Profile ◽  
Hybrid Capture ◽  
Mutational Burden ◽  
Comprehensive Genomic Profiling ◽  
Tumor Mutational Burden ◽  
Tumor Types ◽  
Repair Genes

4533 Background: We performed a CGP to compare the genomic alterations (GA) in ABC, UBC and SCCB. Methods: 143 cases of ACB, 2,142 cases of UCB and 83 cases of SCCB were subjected to CGP using a hybrid-capture based assay. Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. PD-L1 expression was determined by IHC. Results: ABC patients were younger and more often female than UBC and SCCB (P < 0.0001). UBC and SCCB had a higher GA/tumor than ABC (P = 0.01). Un-targetable GA were similar in all 3 groups involving TP53 and KRAS. APC GA were more frequent in ABC whereas TERT, CDKN2A/B and DNA-repair genes ( ARID1A and KDM6A) more frequently altered in UBC and SCCB. Targetable MTOR pathway GA ( PIK3CA, TSC1, PTEN) were more frequent in UBC and SCCB as were targetable kinase alterations ( FGFR3 and ERBB2). The UBC and SCCB had a significantly higher TMB than ABC (P < 0.0001) including mean TMB and TMB > 20 mut/Mb (P < 0.0001). CD274 (PD-L1) was amplified more frequently in SCCB than ACB or UBC (P < 0.0001). MSI high status was very uncommon in all tumor types. Conclusions: Deep sequencing reveals that ABC features a widely different genomic profile from UBC and SCCB. UBC has the highest frequencies of targetable kinase GA and high TMB. SCCB has the highest frequencies of IO efficacy predicting biomarkers including mean TMB and PD-L1 amp. Nonetheless, ABC does feature potential kinase targets such as FGFR3 and ERBB2. [Table: see text]

Comprehensive genomic profiling for chemotherapy-naïve advanced gastrointestinal malignancies.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 832-832
Author(s):  
Tomohiro Kondo ◽  
Quy Pham Nguyen ◽  
Junichi Matsubara ◽  
Keita Fukuyama ◽  
Motoo Nomura ◽  
...  
Keyword(s):  
Clinical Utility ◽  
Genomic Profiling ◽  
Genomic Alterations ◽  
Gastrointestinal Malignancies ◽  
Tract Cancer ◽  
Novel Approach ◽  
Comprehensive Genomic Profiling ◽  
Novel Biomarkers ◽  
Effective Drugs ◽  
Clinical Trial Information

832 Background: From June, 2019, two comprehensive genomic profiling (CGP) assays, "FoundationOne CDx" and “OncoGuide NCC Oncopanel”, were reimbursed by the national insurance system in Japan for patients who were refractory to standard chemotherapy. However, their clinical utility for chemotherapy-naïve cancer patients is unknown. Methods: We conducted a single institutional prospective observational study to evaluate the clinical utility of FoundationOne CDx assay (Cambridge, MA, USA) for the patients with chemotherapy-naïve advanced gastrointestinal malignancies. Patients with adequate H.E. sample were registered in this study. Primary outcome was the detection rate of at least one actionable/druggable cancer genomic alterations. The evidence levels were classified according to clinical practice guidance for next-generation sequencing in cancer diagnosis and treatment (Edition 1.0) (Sunami K. Cancer Sci. 2018). Results: From October 2018 to June 2019, a total of 238 patients were screened and the following 158 patients were registered: colorectal cancer (n = 60), gastric cancer (n = 19), esophageal cancer (n = 23), pancreatic cancer (n = 30), biliary tract cancer (n = 11), rare gastrointestinal malignancies (n = 15). The CGP data were obtained for 113 patients . Median turn-around time was 14 days (range 10-247 days). Actionable/druggable cancer genomic alterations were observed in 113 patients (100%)/ 65 patients (57.5%), respectively. Clinically relevant biomarkers and genomic alterations were identified in 22 patients (19.5%); BRCA2 (n = 4), ERBB2 (n = 4) , BRAF (n = 3) , EGFR (n = 3), FGFR2 (n = 2), MET (n = 2), NTRK (n = 2) , MSI-H (n = 2 ), TMB-high (n = 2), ALK (n = 1) , KIT (n = 1) and ROS1 (n = 1). Of note, novel biomarkers such as ROS1- GOPC fusion and PALB2 rearrangement were obtained in the patients with esophageal squamous cell carcinoma. Conclusions: This is the first study to evaluate the clinical utility of CGP in patient with chemotherapy-naïve advanced gastrointestinal malignancies. Our result indicated that CGP might provide a chance of potentially effective drugs as a novel approach in precision cancer medicine. Clinical trial information: UMIN000034830.

scholarly journals Complete Response of a Colonic High-Grade Neuroendocrine Carcinoma to Platinum-Based Therapy: Insights from Comprehensive Genomic Profiling

2021 ◽  
Author(s):  
Richard Wood ◽  
Daniel Rayson ◽  
Thomas Arnason ◽  
Ryan C DeCoste ◽  
Daniel Gaston ◽  
...  
Keyword(s):  
Neuroendocrine Carcinoma ◽  
Stage Iv ◽  
Large Cell ◽  
Complete Response ◽  
Response To Therapy ◽  
Hereditary Cancer Syndrome ◽  
Genomic Profiling ◽  
Cancer Syndrome ◽  
Optimal Care ◽  
Comprehensive Genomic Profiling

Abstract Background Comprehensive genomic profiling (CGP) is an essential tool in precision medicine, providing diagnostic, prognostic, and predictive (therapeutic) information that enables personalized optimal care for cancer patients. We present the case of a 54-year-old woman with stage IV large-cell neuroendocrine carcinoma (LCNEC) of the colon with liver and nodal metastases with complete response to therapy and demonstrate the value of CGP in identifying potential targets for treatment in these tumors. Results CGP performed on the tumor showed pathogenic mutations in multiple oncogenes and tumor suppressor genes including BRCA1, BAP1, and BRAF, high tumor mutation burden (TMB), and high microsatellite instability (MSI-H). Treatment with platinum-based therapy resulted in a complete radiographic response of the metastases, with no evidence of recurrence after 6.5 years. Assessment by Medical Genetics did not identify any evidence of hereditary cancer syndrome. The dramatic response to therapy is likely due to loss of BRCA1 and/or BAP1 function, as deleterious mutations in both genes predict response to platinum-based therapy through exploitation of deficient homologous recombination repair (HRR). The information provided by CGP also suggested potential tumor sensitivity to poly(ADP-Ribose) polymerase inhibitors (PARPi), immunotherapy (IT) and BRAF/MEK inhibitor therapy, should the tumor recur. Conclusion This case highlights the value of CGP in guiding diagnosis and management of rare and aggressive tumors.

scholarly journals A Pilot Study of Comprehensive Genomic Profiling for Pediatric and Adolescent and Young Adult Solid Tumor Patients in Japan

2021 ◽  
Author(s):  
Shotaro Matsudera ◽  
Yoshihito Kano ◽  
Yasuko Aoyagi ◽  
Kohki Tohyama ◽  
Kei Ogino ◽  
...  
Keyword(s):  
Solid Tumor ◽  
Wilms Tumor ◽  
Adolescent And Young Adult ◽  
Genomic Alteration ◽  
Genomic Profiling ◽  
Tumor Patients ◽  
Comprehensive Genomic Profiling ◽  
Healthcare Insurance ◽  
Tumor Types ◽  
Basket Trials

Background: Comprehensive genomic profiling (CGP) was widely adopted in Japan after its coverage by national healthcare insurance began in June 2019. We investigated the clinical utility of CGP in pediatric and adolescent young adults (AYA) solid tumor patients. Procedure: Between November 2017 and December 2019, 13 patients who progressed with or who were likely to progress with standard therapies were recruited to the PROFILE-F study to undergo CGP using either FoundationOne® CDx or FoundationOne® Heme. Results: The median age was 28 years old. Tumor types were as follows: neuroblastoma (n=1), Wilms’ tumor (n=1), rhabdomyosarcoma (n=2), Ewing sarcoma (n=1), gastric cancer (n=1), rectal cancer (n=1), osteosarcoma (n=1), neuroendocrine tumor (n=2), salivary gland carcinoma (n=1), tracheal adenoid cystic carcinoma (n=1), and thymic cancer (n=1). In 92% of cases, at least one genomic alteration was identified, including CDKN2A (four cases), TP53 (three cases), and MYC (two cases). Actionable aberrations were found in 10 cases (77%), and a clinical trial candidate was found in seven cases (54%). However, no patients were able to receive biomarker-matched therapy according to their genomic alterations. Conclusions: Further efforts to increase basket trials and collection of clinical genomic data to predict response are necessary to advance precision cancer medicine in pediatric and AYA populations.

Comprehensive genomic profiling of parathyroid carcinoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 6088-6088 ◽  
Author(s):  
Hyunseok Kang ◽  
Adrian Daniel Schubert ◽  
Paul Ladenson ◽  
Douglas Wilmot Ball ◽  
Jon Chung ◽  
...  
Keyword(s):  
Parathyroid Carcinoma ◽  
Cell Cycle Progression ◽  
Stage Iv ◽  
Genomic Profiling ◽  
Genomic Alterations ◽  
Initial Surgery ◽  
Mutation Burden ◽  
Number Of Patients ◽  
Comprehensive Genomic Profiling ◽  
Life Threatening

6088 Background: Parathyroid carcinoma (PC) is a rare endocrine malignancy, which can cause life-threatening hypercalcemia. Initial surgery is often noncurative, and adjunctive radiotherapy and previous chemotherapies have not been shown to be effective. Previous studies identified recurring mutations in CDC73 and PRUNE2in a limited number of patients. We queried whether comprehensive genomic profiling (CGP) would have potential to discover novel targets of therapy. Methods: DNA was extracted from 40 microns of FFPE sections from 13 consecutive cases of relapsed/metastatic PC. CGP was performed on hybridization-captured, adaptor ligation based libraries to a mean coverage depth of 672x for up to 315 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer. Genomic alterations (GA) included base substitutions (SUB), INDELs, copy number alterations (CNA) and fusions/rearrangements. Clinically relevant GA (CRGA) were defined as GA linked to drugs on the market or under evaluation in mechanism driven clinical trials. Results: Total of 13 specimens were identified from 7 male and 6 female patients. The mean age of the patients in this study was 54 years (range 38 to 76 years). All (100%) cases were Stage IV at the time of CGP. Tumor mutation burden was generally low - median mutation load per mega base was 1.8. There were 58 total GA (4.5 GA/sample) and 10 CRGA (0.8 CRGA/sample). The most frequent GA were non-CRGA mutations in TP53 (31%) and CDC73 (31%). MEN1 mutations were identified in 23% of cases. Frequent alterations in genes controlling cell cycle progression at G1 including CDKN1B, CDKN2A, CDKN2B and CDKN2C were identified (30%). The most frequent CRGA involved PTEN (23%), NF1 (23%) and KDR (15%). No alterations in BRAF or RETwere identified. A patient with KDR mutation treated with cabozantinib experienced > 50% drop in PTH level and radiographic partial response in 3 months. Conclusions: CGP identified previously unreported TP53 mutations in PCs and potentially actionable genomic alterations including PTEN, NF1 and KDR. Clinical benefit and response observed in a patient treated with VEGFR targeted therapy suggest that patients with this rare tumor may be candidates for targeted therapies.

Comprehensive genomic profiling of relapsed and refractory small cell neuroendocrine carcinoma of the urinary bladder.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 350-350 ◽  
Author(s):  
Sumanta K. Pal ◽  
Jean H. Hoffman-Censits ◽  
Julia Andrea Elvin ◽  
Jo-Anne Vergilio ◽  
James Suh ◽  
...  
Keyword(s):  
Neuroendocrine Carcinoma ◽  
De Novo ◽  
Stage Iv ◽  
Small Cell ◽  
Genomic Profiling ◽  
Small Cell Neuroendocrine Carcinoma ◽  
Ffpe Specimen ◽  
Comprehensive Genomic Profiling ◽  
Carcinoma Of The Bladder ◽  
Copy Number Changes

350 Background: Small cell neuroendocrine carcinoma of the bladder (SCCB) is rare but aggressive form of genitourinary cancer that can arise de novo or in conjunction with urothelial carcinoma (UCB). Methods: DNA was extracted from 40 microns of FFPE specimen from 29 cases of relapsed, refractory and metastatic SCCB and 1,113 UCB. Comprehensive genomic profiling (CGP) was performed using a hybrid-capture, adaptor ligation based next generation sequencing assay to a mean coverage depth of > 503X. Tumor mutational burden (TMB) was calculated from a minimum of 1.11 Mb of sequenced DNA as previously described and reported as mutations/Mb. The results were analyzed for all classes of genomic alterations (GA), including base substitutions, insertions and deletions (short variants; SV), fusions, and copy number changes including amplifications (amp) and homozygous deletions. Results: 29 SCCB cases were confirmed on routine histology and featured positive IHC staining for chromogranin, synaptophysin or both. Patients had a mean age of 68.1 years (range 49-90 years) and 25 (86%) were male. At the time of CGP, 3 (10%) SCCB were Stage III and 26 (90%) were stage IV. The primary SCCB was used for sequencing in 14 (48%) of cases and a metastasis sample in 15 (52%). The 29 SCCB featured 2.86 GA/case.The genomics of SCCB differed significantly from UCB (Table). The most frequent clinically relevant GA in SCCB were RICTOR amp (21%) and PIK3CA (10%), BRCA1, HGF, FBXW7 and CCND2 SV (7% each). The relatively high TMB in SCCB (7% TMB > 20 mut/Mb and 28% TMB > 10 mut/Mb) is similar to that seen in UCB. No SCCB cases were MSI-high. ERBB2 and FGFR1 GA frequencies (both 3%) in SCCB were lower than in similarly studied UCB. Conclusions: SCCB differs in genomic landscape from UCB in having higher frequencies of TP53 and RB1 GA and lower frequencies of FGFR3 and ERBB2 GA. However, like UCB, SCCB shares the presence of multiple GA associated with potential responses to targeted therapies and high TMB associated with response to immune checkpoint inhibitor therapy. [Table: see text]

Anal melanoma: A comparative comprehensive genomic profiling study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9566-9566
Author(s):  
Jeffrey S. Ross ◽  
Russell Madison ◽  
Julia Andrea Elvin ◽  
Jo-Anne Vergilio ◽  
Jonathan Keith Killian ◽  
...  
Keyword(s):  
Uv Light ◽  
Light Exposure ◽  
Mtor Pathway ◽  
Braf V600e ◽  
Genomic Profiling ◽  
Genomic Alterations ◽  
Comprehensive Genomic Profiling ◽  
Tumor Mutational Burden ◽  
Ffpe Tissues ◽  
Tumor Types

9566 Background: We performed a comprehensive genomic profiling (CGP) study of AM and CM to learn of potential genomic alterations (GA) linked to targeted and immune checkpoint inhibitor (ICPI) therapies. Methods: 90 AM and 1804 CM FFPE tissues from late stage underwent hybrid-capture based CGP to evaluate all classes of genomic alterations (GA). Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. PD-L1 expression was determined by IHC. Results: AM and CM had a similar age, but AM females and CM males were significantly more common (P < 0.0001). GA/tumor was significantly higher in CM (UV light exposure) as were the median TMB and frequency of TMB ≥ 10 and 20 mutations/Mb (P < 0.0001 for all comparisons). PD-L1 expression was higher in AM than CM (P = 0.0023). AM and CM were all MS-stable. The contrast in S FB1 mutations in AM and TERT GA in CM were significant (P < 0.0001). Of potentially targetable GA, AM featured significantly more KIT GA than CM (P < 0.0001), whereas CM featured significantly more BRAF GA (P < 0.0001). Only 11% of AM BRAF GA were V600E whereas 74% of CM BRAF GA were V600E (P < 0.0001). MTOR pathway GA were common in both tumor types. Additional potentially targetable alterations in PDGFRA and ERBB2 kinases were seen in AM but not in CM. Conclusions: CM is distinct from AM featuring higher GA/tumor, higher TMB and frequent BRAF V600E GA that predict benefit from ICPI and anti-BRAF therapies. Although both AM and CM feature MTOR pathway targets, AM does have higher PD-L1 expression than CM and is characterized by an array of potentially targetable kinase genes including KIT, PDGFRA, ERBB2 and to a lesser extent than CM, BRAF.[Table: see text]

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