Reference Detail

Ref Type

Journal Article

PMID

(27900369)

Authors

Biswas R, Gao S, Cultraro CM, Maity TK, Venugopalan A, Abdullaev Z, Shaytan AK, Carter CA, Thomas A, Rajan A, Song Y, Pitts S, Chen K, Bass S, Boland J, Hanada KI, Chen J, Meltzer PS, Panchenko AR, Yang JC, Pack S, Giaccone G, Schrump DS, Khan J, Guha U

Title

Genomic profiling of multiple sequentially acquired tumor metastatic sites from an "exceptional responder" lung adenocarcinoma patient reveals extensive genomic heterogeneity and novel somatic variants driving treatment response.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Cold Spring Harbor molecular case studies	2	6	2016 Nov	a001263	Cold Spring Harb Mol Case Stud

URL

Abstract Text

We used next-generation sequencing to identify somatic alterations in multiple metastatic sites from an "exceptional responder" lung adenocarcinoma patient during his 7-yr course of ERBB2-directed therapies. The degree of heterogeneity was unprecedented, with ∼1% similarity between somatic alterations of the lung and lymph nodes. One novel translocation, PLAG1-ACTA2, present in both sites, up-regulated ACTA2 expression. ERBB2, the predominant driver oncogene, was amplified in both sites, more pronounced in the lung, and harbored an L869R mutation in the lymph node. Functional studies showed increased proliferation, migration, metastasis, and resistance to ERBB2-directed therapy because of L869R mutation and increased migration because of ACTA2 overexpression. Within the lung, a nonfunctional CDK12, due to a novel G879V mutation, correlated with down-regulation of DNA damage response genes, causing genomic instability, and sensitivity to chemotherapy. We propose a model whereby a subclone metastasized early from the primary site and evolved independently in lymph nodes.

Filtering

Case insensitive filtering will display rows if any text in any cell matches the filter term
Use simple literal full or partial string matches
Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
Click on any column header arrows to sort by that column
Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description
ABL1	P918S	missense	unknown	ABL1 P918S lies within the DNA-binding domain of the Abl1 protein (UniProt.org). P918S has been identified in the scientific literature (PMID: 27900369), but has not been biochemically characterized and therefore, its effect on Abl1 protein function is unknown (PubMed, Dec 2023).
DNMT3A	P59L	missense	unknown	DNMT3A P59L does not lie within any known functional domains of the Dnmt3a protein (UniProt.org). P59L has been identified in the scientific literature (PMID: 27900369), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Jan 2024).
ROS1	N790S	missense	unknown	ROS1 N790S lies within the extracellular domain of the Ros1 protein (UniProt.org). N790S has been identified in the scientific literature (PMID: 27900369), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024).
ROS1	S1581F	missense	unknown	ROS1 S1581F lies within fibronectin type-III domain 7 of the Ros1 protein (UniProt.org). S1581F has been identified in the scientific literature (PMID: 27900369), but has not been biochemically characterized and therefore, its effect on Ros1 protein function is unknown (PubMed, Mar 2024).

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References