Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0027627 (
metastases
)
103,950
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Purpose:
Malignant pleural mesothelioma (MPM) is an aggressive cancer. Data are not available in prospective trials on correlations between genetic alterations and outcomes of therapies. In this study, we assessed the genetic profile of MPM patients (pts) in tissue samples.
Patients and Methods:
From December 2016 to July 2018 (end of enrolment), 164 pts were enrolled. We evaluated by targeted sequencing the mutational profile of a panel of 34 genes:
ACTB
,
ACTG1
,
ACTG2
,
ACTR1A
,
BAP1
,
CDH8
,
CDK4
,
CDKN2A
,
CDKN2B
,
COL3A1
,
COL5A2
,
CUL1
,
DHFR
,
GOT1
,
KDR
,
KIT
,
MXRA5
,
NF2
,
NFRKB
,
NKX6-2
,
NOD2
,
PCBD2
,
PDZK1IP1
,
PIK3CA
,
PIK3CB
,
PSMD13
,
RAPGEF6
,
RDX
,
SETDB1
,
TAOK1
,
TP53
,
TXNRD1
,
UQCRC1
,
XRCC6.
Genetic profiling was correlated with clinical and pathological variables.
Results:
Overall, 110 pts (67%) from both treatment arms had samples available for molecular analysis. Median age was 63 years (45-81), 25.5% (
n
= 28) were females, and 74.5% (
n
= 82) were males. Tumor histotype was 81.8% (
n
= 90) epithelioid and 18.2% (
n
= 20) non-epithelioid; 28.5% of the tumors (
n
= 42) were stage IV, 71.5% (
n
= 68) were stage III. Targeted sequencing of tissue specimens identified 275 functional somatic mutations in the 34 genes analyzed. The number of mutated genes was positively associated with higher stage and
metastatic disease
(
p
= 0.025).
RDX
(42%),
MXRA5
(23%),
BAP1
(14%), and
NF2
(11%) were the most frequently mutated genes. Mutations in
RAPGEF6
(
p
= 0.03) and
ACTG1
(
p
= 0.02) were associated with the non-epithelioid subtype, and mutations in
BAP1
(
p
= 0.04) were related to progression-free survival (PFS) > 6 months.
Conclusions:
In the Ramucirumab Mesothelioma clinical trial (RAMES), mutation of the gene
BAP1
is related to a prolonged PFS for patients treated with platinum/pemetrexed regimens (
p
= 0.04).
...
PMID:Mutational Profile of Malignant Pleural Mesothelioma (MPM) in the Phase II RAMES Study. 3306 98
