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Targeted sequencing with a customized panel to assess histological typing in endometrial carcinoma
Ist Teil von
Virchows Archiv : an international journal of pathology, 2019-05, Vol.474 (5), p.585-598
Ort / Verlag
Berlin/Heidelberg: Springer Berlin Heidelberg
Erscheinungsjahr
2019
Quelle
MEDLINE
Beschreibungen/Notizen
The two most frequent types of endometrial cancer (EC) are endometrioid (EEC) and serous carcinomas (SC). Differential diagnosis between them is not always easy. A subset of endometrial cancers shows misleading microscopical features, which cause problems in differential diagnosis, and may be a good scenario for next-generation sequencing. Previous studies have assessed the usefulness of targeted sequencing with panels of generic cancer-associated genes in EC histological typing. Based on the analysis of TCGA (The Cancer Genome Atlas), EEC and SC have different mutational profiles. In this proof of principle study, we have performed targeted sequencing analysis with a customized panel, based on the TCGA mutational profile of EEC and SC, in a series of 24 tumors (16 EEC and 8 SC). Our panel comprised coding and non-coding sequences of the following genes:
ABCC9
,
ARID1A
,
ARID5B
,
ATR
,
BCOR
,
CCND1
,
CDH19
,
CHD4
,
COL11A1
,
CSDE1
,
CSMD3
,
CTCF
,
CTNNB1
,
EP300
,
ERBB2
,
FBXW7
,
FGFR2
,
FOXA2
,
KLLN
,
KMT2B
,
KRAS
,
MAP3K4
,
MKI67
,
NRAS
,
PGAP3
,
PIK3CA
,
PIK3R1
,
PPP2R1A
,
PRPF18
,
PTEN
,
RPL22
,
SCARNA11
,
SIN3A
,
SMARCA4
,
SPOP
,
TAF1
,
TP53
,
TSPYL2
,
USP36
, and
WRAP53.
Targeted sequencing validation by Sanger sequencing and immunohistochemistry was performed in a group of genes.
POLE
mutation status was assessed by Sanger sequencing. The most mutated genes were
PTEN
(93.7%),
ARID1A
(68.7%),
PIK3CA
(50%), and
KMT2B
(43.7%) for EEC, and
TP53
(87.5%),
PIK3CA
(50%), and
PPP2R1A
(25%) for SC. Our panel allowed correct classification of all tumors in the two categories (EEC, SC). Coexistence of mutations in
PTEN
,
ARID1A
, and
KMT2B
was diagnostic of EEC. On the other hand, absence of
PTEN
,
ARID1A
, and
KMT2B
mutations in the presence of
TP53
mutation was diagnostic of SC. This proof of concept study demonstrates the suitability of targeted sequencing with a customized endometrial cancer gene panel as an additional tool for confirming histological typing.