Chromothripsis and corresponding cancer gene amplifications and losses. A, Representative Circos plots of SVs and CNAs across the genome by WGS. Outer band shows an ideogram of chromosome positions and cytogenetic bands. Second band depicts total CN, and third band shows minor allele CN. The inner circle depicts SVs as arcs connecting the two relevant genomic points as identified by three algorithms (see “Methods”). CNAs in key cancer genes in the regions of chromothripsis (red, amplifications; blue, deletions) are displayed. Circos plots for all cases are shown in Supplementary Fig. S6. B, CN log ratio plots from the FACETS algorithm displaying the distinctive oscillating CN states on chromosomes with chromothripsis. CN segments are shown in red. Focal segments (<2 MB in size) are shown as enlarged points for visual purposes. Selected amplifications are indicated (yellow). C, Summary of chromosomal location of chromothriptic events in cases analyzed by WGS and tNGS. Also shown are selected amplifications and losses in oncogenes and tumor suppressors, respectively, localized to the chromothriptic chromosomes. Full list is provided in Supplementary Table S7. D, Schematic summary for the rate of major genomic mechanisms detected in the set analyzed by WGS (n = 11) and in the full cohort (n = 20). In the lower diagram, major chromosomes involved by chromothripsis are indicated in the inner doughnut, and corresponding recurrent gene amplifications are indicated in the outer doughnut. E, Total number of SVs identified in samples analyzed by WGS. Variants are color-coded by type. F, Number of fusions predicted in samples with available RNA-seq. G, Diagram illustrating putative enhancer hijacking in case A17 with chromothripsis on chromosome 2 resulting in translocation between SH3RF3 on chromosome 2 and upstream regulatory region of CCND1 on chromosome 11. Epigenetic landscape surrounding the breakpoint was extrapolated from data from multiple tissue types (Epilogos search tool). ChrT, chromothripsis.

Chromothripsis

10.1158/2159-8290.28193775

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RUNX2 (6p21.1) amplification in osteosarcoma

Human Pathology (2019)

Sounak Gupta Tatsuo Ito Deepu Alex Chad Vanderbilt Jason C. Chang

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10.1016/j.humpath.2019.09.010

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Next-Generation Sequencing–Based Assessment of JAK2, PD-L1, and PD-L2 Copy Number Alterations at 9p24.1 in Breast Cancer

Journal of Molecular Diagnostics (2018)

Sounak Gupta Chad Vanderbilt Paolo Cotzia Javier Arias‐Stella Jason C. Chang

Genomic amplification at 9p24.1, including the loci for JAK2, PD-L1, and PD-L2, has recently been described as a mechanism of resistance in postchemotherapy, triple-negative breast cancer. This genomic signature holds significant promise as a prognostic biomarker and has implications for targeted therapy with JAK2 inhibitors, as well as with immunotherapy. To guide future screening strategies, the frequency of these alterations was determined. A total of 5399 cases were included in the study. This encompassed 2890 institutional cases tested by the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets assay and 2509 cases from The Cancer Genome Atlas (TCGA). The combined incidence of 9p24.1 amplifications in both the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets and TCGA cohorts was 1.0% (56/5399 cases) and showed a >10-fold higher incidence in triple-negative breast cancer (triple-negative: 5.1%; non–triple-negative: 0.5%). Tumor mutation burden and stromal tumor infiltrating lymphocytes, parameters used to assess response to immunotherapy, were not significantly higher for these cases. The significance of genomic losses at 9p24.1 is unclear, and further studies are needed. Herein, we studied the spectrum of copy number alterations in breast cancer cases within our institutional clinical sequencing cohort and those profiled by TCGA to determine the frequency of genomic alterations that may predict response or resistance to JAK2 inhibitors and/or immunotherapy.

10.1016/j.jmoldx.2018.10.006

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Supplemental Figure 1 from Comprehensive Molecular and Clinicopathologic Analysis of 200 Pulmonary Invasive Mucinous Adenocarcinomas Identifies Distinct Characteristics of Molecular Subtypes

Jason C. Chang Michael Offin Christina J. Falcon David Brown Brian Houck‐Loomis

Supplemental Figure 1. Consort diagram summarizing the molecular workflow of cases.

Pulmonary adenocarcinoma

10.1158/1078-0432.22480635

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Supplementary Table 2 from Tumor Analyses Reveal Squamous Transformation and Off-Target Alterations As Early Resistance Mechanisms to First-line Osimertinib in EGFR-Mutant Lung Cancer

Adam J. Schoenfeld Joseph Chan Daisuke Kubota Hiroki Sato Hira Rizvi

Supplemental Table 2. Primer sequences

Osimertinib

10.1158/1078-0432.22478843.v1

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The Genomic Landscape of SMARCA4 Alterations and Associations with Outcomes in Patients with Lung Cancer

Clinical Cancer Research (2020)

Adam J. Schoenfeld Chai Bandlamudi Jessica A. Lavery Joseph Montecalvo Azadeh Namakydoust

mutations are among the most common recurrent alterations in non-small cell lung cancer (NSCLC), but the relationship to other genomic abnormalities and clinical impact has not been established.

SMARCA4

10.1158/1078-0432.ccr-20-1825

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A07 The Genomic Landscape of SMARCA4 Alterations and Association with Patient Outcomes in Lung Cancer

Journal of Thoracic Oncology (2020)

Adam J. Schoenfeld Joseph Montecalvo Azadeh Namakydoust Jessica A. Lavery Chai Bandlamudi

SMARCA4

STK11

ARID1A

10.1016/j.jtho.2019.12.036

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