Rajiv Gandhi Cancer Institute and Research Center

Sector-5, Rohini,
New Delhi-110085
http://www.rgcirc.org/

Date: 29 Jan 2019 1 of 5

 
Sample Information
Name. MRS. KALPANA JAIN
CR No.: 201942
Age/Sex. 55/Female
Referred Doctor. Dr. Sumit Goyal / Dr. Manish Sharma
OPD/IPD. IPD
I.P. NO. 19/IP309099
Sample Type. B/11899/2019/001/001-001
Test Description. - This panel is a multibiomarker next generation sequencing assay that enables detection of 52 genes. This panel
are CE-IVD* next generation sequencing (NGS) for both DNA and RNA workflows, enabling analysis of solid tumour formalin-fixed,
paraffinembedded (FFPE) samples). It is detect multiple types of varients, including hotspots, single nucleotide variants (SNVs), indels,
copy number variants (CNVs), and gene fusions. Copy Number: Pass Quality Control: Pass
Gene Analyzed - AKT1, ALK, AR, BRAF, CDK4, CTNNB1, DDR2, EGFR, ERBB2, ERBB3, ERBB4, ESR1, FGFR2, FGFR3, GNA11, GNAQ, HRAS,
IDH1, IDH2, JAK1, JAK2, JAK3, KIT, KRAS, MAP2K1, MAP2K2, MET, MTOR, NRAS, PDGFRA, PIK3CA, RAF1, RET, ROS1, SMO.
Focal Copy Number Variants - ALK, AR, BRAF, CCND1, CDK4,CDK6, EGFR, ERBB2, FGFR1, FGFR2, FGFR3, FGFR4, KIT, KRAS, MET, MYC,
MYCN, PDGFRA, PIK3CA.
Fusion Transcripts Analyzed - ABL1, AKT3, ALK, AXL, BRAF, EGFR, ERBB2, ERG, ETV1, ETV4, ETV5, FGFR1, FGFR2, FGFR3, MET, NTRK1,
NTRK2, NTRK3, PDGFRA, PPARG, RAF1, RET, ROS1, SMO.
Allele Frequency and Coverage - More than equal to 5 percentage and coverage is more than equal to 500x.
Clinical Interpretation. - The RET gene has been reported as a translocation/fusion partner of a variety of genes, including KIF5B,
CCDC6, TRIM33, CUX1, KIAA1468, NCOA4, BCR, FGFR1OP. The RET translocations result in chimeric proteins where the intracellular
kinase domain of RET is fused to upstream dimerization domains provided by the various translocation partners, creating a protein
characterized by spontaneous dimerization and constitutive signaling (PubMed: 24561444). Function al studies have identified such
RET fusion genes as pathogenic gain-of-function mutations resulting in transformation in vitro and in vivo (PubMed: 22327623,
25064355). RET translocations have been previously reported in other salivary gland tumors like Secretory carcinoma and Salivary duct
Carcinoma but not in Adenoid Cystic Carcinoma. Therapeutic trial for RET translocation drugs should be based on clinical judgment.
References. - PubMed: 24561444; PubMed: 22327623; PubMed: 25064355.

Sample Cancer Type: Metastatic

Other Solid TumorCystic Carcinoma
Adenoid

Table of Contents Report Highlights

Variant Details 2 1 Clinically Significant Biomarkers
Relevant Therapy Summary 2 2 Therapies Available
Relevant Therapy Details 3 2 Clinical Trials
Clinical Trials 4

Clinically Significant Biomarkers      Indicated       Contraindicated

 
Relevant Therapies Relevant Therapies
Genomic Alteration (In this cancer type) (In other cancer type) Clinical Trials

CCDC6-RET fusion None cabozantinib 2

coiled-coil domain containing 6 - ret proto-oncogene vandetanib
 
Sources included in relevant therapies: EMA1, FDA2, ESMO, NCCN

Prevalent cancer biomarkers without clinical significance based on included data sources
FGFR1 amplification

© 2018 Thermo Fisher Scientific Inc. All rights reserved.

Disclaimer: The data presented here is a result of the curation of published data sources, but may not be exhaustive. The data version is 2018.09(005).
 Rajiv Gandhi Cancer Institute and Research Center
Sector-5, Rohini,
New Delhi-110085
http://www.rgcirc.org/

Date: 29 Jan 2019 2 of 5

 

Variant Details
DNA Sequence Variants
 
Allele
Gene Amino Acid Change Coding Variant ID Locus Frequency Transcript Variant Effect
ALK p.(D1529E) c.4587C>G . chr2:29416366 49.45% NM_004304.4 missense

ALK p.(I1461V) c.4381A>G . chr2:29416572 99.75% NM_004304.4 missense

ALK p.(=) c.3375C>A . chr2:29445458 98.94% NM_004304.4 synonymous

FGFR3 p.(=) c.1953G>A . chr4:1807894 99.80% NM_000142.4 synonymous

PDGFRA p.(=) c.1701A>G . chr4:55141055 99.95% NM_006206.5 synonymous

FGFR4 p.(P136L) c.407C>T . chr5:176517797 15.88% NM_213647.2 missense

FGFR4 p.(=) c.483A>G . chr5:176517985 35.56% NM_213647.2 synonymous

FGFR4 p.(=) c.1659C>T . chr5:176522562 14.46% NM_213647.2 synonymous

EGFR p.(=) c.2361G>A . chr7:55249063 8.55% NM_005228.4 synonymous

RET p.(=) c.2307G>T . chr10:43613843 47.97% NM_020975.4 synonymous

 
Gene Fusions (RNA)
 
Genes Variant ID Locus
CCDC6-RET CCDC6-RET.C1R12.COSF1271 chr10:61665880 - chr10:43612032 (pathogenic)
 
Copy Number Variations
 
Gene Locus Copy Number
FGFR1 chr8:38271445 5.74 (pathogenic)
 

Relevant Therapy Summary

 
 In this cancer type  In other cancer  In this cancer type and  Contraindicated  Both for use and  No evidence
type other cancer types contraindicated
 
CCDC6-RET fusion

Relevant Therapy EMA FDA ESMO NCCN Clinical Trials*

vandetanib      (IV)
cabozantinib     
alectinib      (IV)
 
* Most advanced phase (IV, III, II/III, II, I/II, I) is shown and multiple clinical trials may be available.

© 2018 Thermo Fisher Scientific Inc. All rights reserved.

Disclaimer: The data presented here is a result of the curation of published data sources, but may not be exhaustive. The data version is 2018.09(005).
 Rajiv Gandhi Cancer Institute and Research Center
Sector-5, Rohini,
New Delhi-110085
http://www.rgcirc.org/

Date: 29 Jan 2019 3 of 5

 
Relevant Therapy Details
Current NCCN Information
 
 In this cancer type  In other cancer type  In this cancer type and  Contraindicated  Not recommended  Resistance
other cancer types

NCCN information is current as of 2018-05-15. For the most up-to-date information, search www.nccn.org.
For NCCN International Adaptations & Translations, search www.nccn.org/global/international_adaptations.aspx.

CCDC6-RET fusion
 

 cabozantinib
Cancer type: Non-Small Cell Lung Cancer Variant class: RET fusion
NCCN Recommendation category: 2A

Population segment (Line of therapy):

 Non-Small Cell Lung Cancer; Emerging targeted agents

Reference: NCCN Guidelines® - NCCN-Non-Small Cell Lung Cancer [Version 4.2018]

 
 

 vandetanib
Cancer type: Non-Small Cell Lung Cancer Variant class: RET fusion
NCCN Recommendation category: 2A

Population segment (Line of therapy):

 Non-Small Cell Lung Cancer; Emerging targeted agents

Reference: NCCN Guidelines® - NCCN-Non-Small Cell Lung Cancer [Version 4.2018]

 

© 2018 Thermo Fisher Scientific Inc. All rights reserved.

Disclaimer: The data presented here is a result of the curation of published data sources, but may not be exhaustive. The data version is 2018.09(005).
 Rajiv Gandhi Cancer Institute and Research Center
Sector-5, Rohini,
New Delhi-110085
http://www.rgcirc.org/

Date: 29 Jan 2019 4 of 5

 
Current Clinical Trials Information
Clinical Trials information is current as of 2018-06-01. For the most up-to-date information regarding a particular trial, search
www.clinicaltrials.gov by NCT ID or search local clinical trials authority website by local identifier listed in 'Other identifiers'.

CCDC6-RET fusion
 

No NCT ID - see other identifier(s) Other identifier: UMIN000021802

Research For Elucidating The Resistance
Mechanism To RET Tyrosine Kinase
Inhibitors In Patients With Non-Small-Cell
Lung Cancer Harboring With RET Fusion
Gene
Population segments: Line of therapy N/A, Stage III, Stage IV
Exclusion criteria variant classes: ALK fusion (Non-Small Cell Lung Cancer), EGFR
mutation (Non-Small Cell Lung Cancer)

Cancer type: Non-Small Cell Lung Cancer Phase: IV

Variant class: RET fusion Therapy: alectinib

Location: Japan
 
 

NCT01945762 Other identifiers: Caprelsa104, D4200C00104, NCRN - 2376, OBS14778, UKCRN ID

European, Observational, Prospective 15014
Study to Evaluate the Benefit/Risk of
Vandetanib in RET Mutation Negative Population segments: Line of therapy N/A, Locally advanced, Medullary, Metastatic,
and Positive Patients With Symptomatic, Unresectable
Aggressive, Sporadic, Unresectable,
Locally Advanced/Metastatic Medullary Phase: IV
Thyroid Cancer
Therapy: vandetanib
Cancer type: Thyroid Cancer
Locations: France, Germany, Italy, Netherlands, Spain, United Kingdom
Variant class: RET positive
 

Evidence Summary by Variant Class

A variant class hierarchy was created to summarize gene variants with associated clinical evidence. Evidence items refers to citations
across the different global data sources.

 
CCDC6-RET fusion
 

Evidence
Variant Class Items

RET aberration 0

RET positive 1


RET fusion 3


© 2018 Thermo Fisher Scientific Inc. All rights reserved.

Disclaimer: The data presented here is a result of the curation of published data sources, but may not be exhaustive. The data version is 2018.09(005).
 Rajiv Gandhi Cancer Institute and Research Center
Sector-5, Rohini,
New Delhi-110085
http://www.rgcirc.org/

Date: 29 Jan 2019 5 of 5

 
Evidence Summary by Variant Class (continued)
A variant class hierarchy was created to summarize gene variants with associated clinical evidence. Evidence items refers to citations
across the different global data sources.

 
FGFR1 amplification
 

Evidence
Variant Class Items

FGF pathway 0

FGFR aberration 0


FGFR amplification 0


FGFR1 amplification 0


FGFR1 aberration 0


FGFR1 amplification 0


FGFR pathway 0

FGFR aberration 0


FGFR amplification 0


FGFR1 amplification 0


FGFR1 aberration 0


FGFR1 amplification 0


 
Note: This information in this report does not constitute a treatment recommendation or not to use any specific therapeutic agent, and should not be
interpreted as treatment advice. Decisions concerning patient care and treatment rest solely within the discretion of the patient's treating physician.

Dr. Moushumi Suryavanshi

Senior Consultant
Rajiv Gandhi Cancer Institute & Research Centre
Rohini, New Delhi

© 2018 Thermo Fisher Scientific Inc. All rights reserved.

Disclaimer: The data presented here is a result of the curation of published data sources, but may not be exhaustive. The data version is 2018.09(005).