uu.seUppsala universitets publikasjoner
Endre søk
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Mathematical modeling of disease dynamics in SDHB- and SDHD-related paraganglioma: Further step in understanding hereditary tumor differences and future therapeutic strategies.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.ORCID-id: 0000-0003-0677-4894
Vise andre og tillknytning
2018 (engelsk)Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 8, artikkel-id e0201303Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Succinate dehydrogenase subunit B and D (SDHB and SDHD) mutations represent the most frequent cause of hereditary pheochromocytoma and paraganglioma (PPGL). Although truncation of the succinate dehydrogenase complex is thought to be the disease causing mechanism in both disorders, SDHB and SDHD patients exihibit different phenotypes. These phenotypic differences are currently unexplained by molecular genetics. The aim of this study is to compare disease dynamics in these two conditions via a Markov chain model based on 4 clinically-defined steady states. Our model corroborates at the population level phenotypic observations in SDHB and SDHD carriers and suggests potential explanations associated with the probabilities of disease maintenance and regression. In SDHB-related syndrome, PPGL maintenance seems to be reduced compared to SDHD (p = 0.04 vs 0.95) due to higher probability of tumor cell regression in SDHB vs SDHD (p = 0.87 vs 0.00). However, when SDHB-tumors give rise to metastases, metastatic cells are able to thrive with decreased probability of regression compared with SDHD counterparts (p = 0.17 vs 0.89). By constrast, almost all SDHD patients develop PGL (mainly head and neck) that persist throughout their lifetime. However, compared to SDHB, maintenance of metastatic lesions seems to be less effective for SDHD (p = 0.83 vs 0.11). These findings align with data suggesting that SDHD-related PPGL require less genetic events for tumor initiation and maintenance compared to those related to SDHB, but fail to initiate biology that promotes metastatic spread and metastatic cell survival in host tissues. By contrast, the higher number of genetic abnormalities required for tumor initiation and maintenance in SDHB PPGL result in a lower penetrance of PGL, but when cells give rise to metastases they are assumed to be better adapted to sustain survival. These proposed differences in disease progression dynamics between SDHB and SDHD diseases provide new cues for future exploration of SDHx PPGL behavior, offering considerations for future specific therapeutic and prevention strategies.

sted, utgiver, år, opplag, sider
2018. Vol. 13, nr 8, artikkel-id e0201303
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-363617DOI: 10.1371/journal.pone.0201303ISI: 000441662800006PubMedID: 30106970OAI: oai:DiVA.org:uu-363617DiVA, id: diva2:1256993
Tilgjengelig fra: 2018-10-18 Laget: 2018-10-18 Sist oppdatert: 2019-10-30bibliografisk kontrollert

Open Access i DiVA

fulltext(1416 kB)71 nedlastinger
Filinformasjon
Fil FULLTEXT01.pdfFilstørrelse 1416 kBChecksum SHA-512
f523e8f967bd1323c33471b634027e725985f78950c49726eeda236374974dd7917d1f287f22e1f9d2fed6ecead627779fb28fae97169c65e40763c4b7ac7662
Type fulltextMimetype application/pdf

Andre lenker

Forlagets fulltekstPubMed

Personposter BETA

Crona, Joakim

Søk i DiVA

Av forfatter/redaktør
Crona, Joakim
Av organisasjonen
I samme tidsskrift
PLoS ONE

Søk utenfor DiVA

GoogleGoogle Scholar
Totalt: 71 nedlastinger
Antall nedlastinger er summen av alle nedlastinger av alle fulltekster. Det kan for eksempel være tidligere versjoner som er ikke lenger tilgjengelige

doi
pubmed
urn-nbn

Altmetric

doi
pubmed
urn-nbn
Totalt: 166 treff
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf