Distinct gene expression profiles in ovarian cancer linked to Lynch syndrome.

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Distinct gene expression profiles in ovarian cancer linked to Lynch syndrome. / Jönsson, Jenny-Maria; Bartuma, Katarina; Dominguez, Mev; Harbst, Katja; Ketabi, Zohreh; Malander, Susanne; Jönsson, Mats; Carneiro, Ana; Måsbäck, Anna; Jönsson, Göran B; Nilbert, Mef.

I: Familial Cancer, Vol. 13, Nr. 4, 2014, s. 537-545.

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Jönsson, Jenny-Maria ; Bartuma, Katarina ; Dominguez, Mev ; Harbst, Katja ; Ketabi, Zohreh ; Malander, Susanne ; Jönsson, Mats ; Carneiro, Ana ; Måsbäck, Anna ; Jönsson, Göran B ; Nilbert, Mef. / Distinct gene expression profiles in ovarian cancer linked to Lynch syndrome. I: Familial Cancer. 2014 ; Vol. 13, Nr. 4. s. 537-545.

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TY - JOUR

T1 - Distinct gene expression profiles in ovarian cancer linked to Lynch syndrome.

AU - Jönsson, Jenny-Maria

AU - Bartuma, Katarina

AU - Dominguez, Mev

AU - Harbst, Katja

AU - Ketabi, Zohreh

AU - Malander, Susanne

AU - Jönsson, Mats

AU - Carneiro, Ana

AU - Måsbäck, Anna

AU - Jönsson, Göran B

AU - Nilbert, Mef

PY - 2014

Y1 - 2014

N2 - Ovarian cancer linked to Lynch syndrome represents a rare subset that typically presents at young age as early-stage tumors with an overrepresentation of endometrioid and clear cell histologies. We investigated the molecular profiles of Lynch syndrome-associated and sporadic ovarian cancer with the aim to identify key discriminators and central tumorigenic mechanisms in hereditary ovarian cancer. Global gene expression profiling using whole-genome c-DNA-mediated Annealing, Selection, extension, and Ligation was applied to 48 histopathologically matched Lynch syndrome-associated and sporadic ovarian cancers. Lynch syndrome-associated and sporadic ovarian cancers differed by 349 significantly deregulated genes, including PTPRH, BIRC3, SHH and TNFRSF6B. The genes involved were predominantly linked to cell growth, proliferation, and cell-to-cell signaling and interaction. When stratified for histologic subtype, hierarchical clustering confirmed distinct differences related to heredity in the endometrioid and serous subtypes. Furthermore, separate clustering was achieved in an independent, publically available data set. The distinct genetic signatures in Lynch syndrome-associated and sporadic ovarian cancers point to alternative preferred tumorigenic routes and suggest that genetic discriminators may be relevant for molecular diagnostics and targeted therapeutics.

AB - Ovarian cancer linked to Lynch syndrome represents a rare subset that typically presents at young age as early-stage tumors with an overrepresentation of endometrioid and clear cell histologies. We investigated the molecular profiles of Lynch syndrome-associated and sporadic ovarian cancer with the aim to identify key discriminators and central tumorigenic mechanisms in hereditary ovarian cancer. Global gene expression profiling using whole-genome c-DNA-mediated Annealing, Selection, extension, and Ligation was applied to 48 histopathologically matched Lynch syndrome-associated and sporadic ovarian cancers. Lynch syndrome-associated and sporadic ovarian cancers differed by 349 significantly deregulated genes, including PTPRH, BIRC3, SHH and TNFRSF6B. The genes involved were predominantly linked to cell growth, proliferation, and cell-to-cell signaling and interaction. When stratified for histologic subtype, hierarchical clustering confirmed distinct differences related to heredity in the endometrioid and serous subtypes. Furthermore, separate clustering was achieved in an independent, publically available data set. The distinct genetic signatures in Lynch syndrome-associated and sporadic ovarian cancers point to alternative preferred tumorigenic routes and suggest that genetic discriminators may be relevant for molecular diagnostics and targeted therapeutics.

U2 - 10.1007/s10689-014-9728-1

DO - 10.1007/s10689-014-9728-1

M3 - Article

C2 - 24848881

VL - 13

SP - 537

EP - 545

JO - Familial Cancer

JF - Familial Cancer

SN - 1389-9600

IS - 4

ER -