CC-SIGN® Head & Neck Gene Fusion Next-Generation Sequencing Panel

CC-SIGN^® Head & Neck Gene Fusion Next-Generation Sequencing Panel

This customized, 30-gene Next-Generation Sequencing (NGS)-based laboratory-developed test is intended for use in the diagnosis and management of benign and malignant tumors of the head and neck.

In particular, salivary gland neoplasms are broadly covered by this panel—which also covers select mesenchymal tumors and other lesions arising in head and neck sites.

The CC-SIGN^® Head & Neck Gene Fusion NGS Panel is available as part of a comprehensive, diagnostic consultation or as a stand-alone test. This laboratory-developed test interrogates gene targets associated with known translocations in salivary gland and other solid tumors. Additionally, this panel identifies the corresponding fusion partner which may be helpful in the selection of treatment targets in some cases.

Results are delivered within 14 days of specimen receipt, allowing for a timely, definitive diagnosis in difficult salivary gland tumors and other head and neck lesions in a stand-alone fashion or with the support of our expert pathologists.

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Molecular Pathology at Cleveland Clinic

Test Overview

Test Name

Head and Neck Next Generation Sequencing (HDNK)

CPT Codes

81445
88381

Turnaround Time

14 days (upon specimen receipt)

Specimen Requirements

Formalin-fixed, paraffin-embedded (FFPE) tissue
• Ten (10) unstained, 4 μM sections of FFPE on charged, unbaked slides
• One (1) H&E stained slide with best tumor area* circled by a pathologist

*minimum of 20% tumor content for best results

Transport Temperature

Room (ambient) temperature

Specimen Shipping Address

Cleveland Clinic Laboratories
2119 E. 93^rd Street, L15
Cleveland, OH 44106

Specimens must be sent via UPS, FedEx, or DHL – review our Shipping Information for more details.

Clinical Indications

This test is intended for the diagnosis of benign or malignant mesenchymal tumors (sarcomas & their mimics) as well as other solid tumors.

Targeted Gene Regions

Genes interrogated, including relevant transcripts and exons, are listed in alphabetical order.

A

Gene, Transcript, Exons

ALK
NM_004304
2, 4, 6, 10, 16-23, 25, 26

B

Gene, Transcript, Exons

BRAF
NM_004333
Exons 1-5, 7-16, 18

C

Gene, Transcript, Exons

CAMTA1
NM_015215
Exons 3, 8-10

CRTC1
NM_015321
Exons 1-4

E

Gene, Transcript, Exons

ETV6
NM_001987
Exons 1-7

EWSR1
NM_005243
Exons 4-14

F

Gene, Transcript, Exons

FOS
NM_005252
Exon 4

FOSB
NM_006732
Exons 1, 2

FOXO1
NM_002015
Exons 1-3

FUS
NM_004960
Exons 3-11, 13, 14

G

Gene, Transcript, Exons

GLI1
NM_005269
Exons 4-7

H

Gene, Transcript, Exons

HMGA2
NM_003483
Exons 1-5

M

Gene, Transcript, Exons

MAML2
NM_032427
Exons 2, 3

MKL2
NM_014048
Exons 11-13

MYB
NM_001130173
Exons 7-9, 11-16

N

Gene, Transcript, Exons

NCOA1
NM_147223
Exons 12-15

NR4A3
NM_006981
Exon 2

NR4A3
NM_173200
Exons 3, 4

NTRK1*
NM_002529
Exons 2, 4, 6, 8, 10-14

NTRK2*
NM_006180
Exons 5, 7, 9, 11-18

NTRK3*
NM_001007156
Exon 15

NTRK3*
NM_002530
Exons 4, 7, 10, 12-16

NUTM1
NM_175741
Exons 2-4, 6

*A specimen positive for a fusion in one of these genes makes the patient a candidate for larotrectinib treatment.
Standalone NTRK testing is also available via the CC-SIGN® NTRK Gene Fusion NGS Panel.

P

Gene, Transcript, Exons

PAX3
NM_181459
Exons 6-8

PAX7
NM_002584
Exons 6-8

PLAG1
NM_002655
Exons 1-4

PRKD1
NM_002742
Exons 10-13

R

Gene, Transcript, Exons

RET
NM_020630
Exons 2, 4, 6, 11, 15, 16

RET
NM_020975
Exons 8-14

S

Gene, Transcript, Exons

SS18
NM_001007559
Exons 2-6, 8-11

SS18
NM_005637
Exons 2, 3

STAT6
NM_001178078
Exons 1-7, 15-20

T

Gene, Transcript, Exons

TFE3
NM_006521
Exons 2-8

Y

Gene, Transcript, Exons

YAP1
NM_001130145
Exons 1-9

Pathology Insights – NUT Carcinoma with Sanjay Mukhopadhyay, MD

Pathology Insights Video Series

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Presented by Sanjay Mukhopadhyay, MD

In this video, Sanjay Mukhopadhyay, MD, Director of Pulmonary Pathology at Cleveland Clinic, highlights a rare, aggressive, malignant tumor and draws attention to a distinctive immunohistochemical profile that can serve as a tip-off to the correct diagnosis.

**As part of our educational mission for our clients and communities, Cleveland Clinic Laboratories presents the Pathology Insights video series.**

These short videos break down information about interesting pathology cases to better inform doctors, laboratory staff, patients, or anyone interested in the field of pathology. Each episode features important cases, methods, and practices that are personally presented by our staff pathologists.

Pathology Insights – Diagnosis of CD30+ T-cell Lymphoproliferative Disorders with Genevieve Crane, MD, PhD

Pathology Insights Video Series

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Presented by Genevieve Crane, MD, PhD

The diagnosis of CD30+ T-cell lymphoproliferative disorders, including ALK+ and ALK-negative forms of anaplastic large cell lymphoma, can present challenges. These entities show overlapping morphologic and immunohistochemical features but can vary widely in terms of clinical aggression.

Dr. Genevieve Crane, Staff Hematopathologist at Cleveland Clinic, discusses clinical presentation, morphologic features, and emerging prognostic markers that may aid in diagnosis and clinical management.

**As part of our educational mission for our clients and communities, Cleveland Clinic Laboratories presents the Pathology Insights video series.**

These short videos break down information about interesting pathology cases to better inform doctors, laboratory staff, patients, or anyone interested in the field of pathology. Each episode features important cases, methods, and practices that are personally presented by our staff pathologists.

Pathology Insights – Two Diagnoses in One Bone Marrow with Megan Nakashima, MD

Pathology Insights Video Series

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Presented by Megan Nakashima, MD

Analysis of a bone marrow requires both careful morphologic examination as well as appropriate ancillary studies.

Dr. Megan Nakashima, Staff Hematopathologist at Cleveland Clinic, discusses a complicated bone marrow case involving a patient with thrombocytopenia, monocytosis, and diarrhea. After requiring the incorporation of molecular and immunophenotypic information, two diagnoses are reached.

In addition to this case, Dr. Nakashima reviews relevant changes in the WHO 2016 classification of myeloid and associated neoplasms.

**As part of our educational mission for our clients and communities, Cleveland Clinic Laboratories presents the Pathology Insights video series.**

These short videos break down information about interesting pathology cases to better inform doctors, laboratory staff, patients, or anyone interested in the field of pathology. Each episode features important cases, methods, and practices that are personally presented by our staff pathologists.

Pathology Insights – Diagnosing Microinvasive Breast Cancer with Miglena Komforti, DO

Pathology Insights Video Series

Diagnosing Microinvasive Breast Cancer in a Background of Intraductal Carcinoma

Presented by Miglena Komforti, DO

In the breast, the pathologic diagnosis of a small focus of invasion can be quite challenging.

Dr. Miglena Komforti discusses the histopathologic findings, ancillary immunohistochemical stains, and clinical significance of microinvasive cancer of the breast.

**As part of our educational mission for our clients and communities, Cleveland Clinic Laboratories presents the Pathology Insights video series.**

These short videos break down information about interesting pathology cases to better inform doctors, laboratory staff, patients, or anyone interested in the field of pathology. Each episode features important cases, methods, and practices that are personally presented by our staff pathologists.

Pathology Insights – Diagnosis of Metastatic Renal Cancer with Sean Williamson, MD

Pathology Insights Video Series

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**As part of our educational mission for our clients and communities, Cleveland Clinic Laboratories presents the Pathology Insights video series.**

These short videos break down information about interesting pathology cases to better inform doctors, laboratory staff, patients, or anyone interested in the field of pathology. Each episode features important cases, methods, and practices that are personally presented by our staff pathologists.

Pathology Insights – Pathology of Vaping-Associated Lung Injury with Sanjay Mukhopadhyay, MD

Pathology Insights Video Series

Pathology of Vaping-Associated Lung Injury

Presented by Sanjay Mukhopadhyay, MD

Sanjay Mukhopadhyay, MD, discusses the findings of a study on the lung pathology of vaping.

Featured in an article co-authored by Dr. Mukhopadhyay and published in the American Journal of Clinical Pathology, the study focuses on the results of microscopic examination of biopsied lung tissue from individuals who developed severe lung illness associated with vaping.

This is one of the first case series in the world to examine lung biopsies from patients with vaping-associated lung illness and is the first-ever study on vaping published in a pathology journal. These findings have important public health implications and are detailed in the video.

**As part of our educational mission for our clients and communities, Cleveland Clinic Laboratories presents the Pathology Insights video series.**

These short videos break down information about interesting pathology cases to better inform doctors, laboratory staff, patients, or anyone interested in the field of pathology. Each episode features important cases, methods, and practices that are personally presented by our staff pathologists.

CC-SIGN® NTRK Plus Gene Fusion Next-Generation Sequencing Panel

CC-SIGN^® NTRK Gene Fusion Next-Generation Sequencing Panel

This NGS-based laboratory-developed test is designed to detect fusion events in NTRK1, NTRK2, and NTRK3, regardless of fusion partner.

Clinical information obtained from the CC-SIGN^® NTRK Gene Fusion NGS Panel can determine if a patient is a candidate for TRK tyrosine kinase inhibitor treatment.

The US Food and Drug Administration (FDA) has approved the use of first-generation TRK tyrosine kinase inhibitors—including larotrectinib (Vitrakvi^®) and entrectinib (Rozlytrek^®)—to treat patients whose tumors harbor NTRK1, NTRK2, or NTRK3 fusions.

Request a Pathology Consult

Molecular Pathology at Cleveland Clinic

NTRK Fusions are Clinically Actionable

TRK tyrosine kinase inhibitors, such as larotrectinib and entrectinib, are drugs utilized to treat solid tumors with a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation. These drugs provide a treatment option to patients with no satisfactory alternative therapies or whose cancer has progressed following treatment, specifically in cases that are either metastatic or where surgical resection is likely to result in severe morbidity.^1,2 This treatment targets cancers with NTRK fusions and is not limited by tissue or tumor type.

1. U.S. Food & Drug Administration. FDA approves larotrectinib for solid tumors with NTRK gene fusions. Available at https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm626720.htm. [Online] Updated Dec 17, 2018.
2. U.S. Food & Drug Administration. FDA approves entrectinib for NTRK solid tumors and ROS-1 NSCLC. Available at https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-entrectinibntrk-solid-tumors-and-ros-1-nsclc [Online] Updated Aug 16, 2019.