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- Martin de la Fuente, Laura, et al.
(författare)
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Copy number signatures for early diagnosis of high-grade serous ovarian carcinoma
- 2022
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundThe detection of ovarian carcinoma-derived somatic mutations in cervical samples and uterine lavages in several studies since 2013, has brought hope for the development of new biomarkers for early detection. High-grade serous ovarian carcinoma (HGSC) is strongly dominated by copy number alterations (CNAs). These CNAs are the consequence of underlying mutational processes in HGSC. We interrogated CNAs from low coverage whole-genome sequencing (WGS) data in HGSC tumors, plasma, endometrial biopsies, and cervical samples to explore if copy number signatures can be used as a biomarker for early detection of HGSC.Methods A total of 204 samples were included from 18 patients with HGSC, four BRCA mutation carriers and seven benign controls. Estimations of ploidy and cellularity, and thus calculation of absolute copy number, were optimized through a combination of the ACE, Rascal, and ichorCNA bioinformatic tools. Mixture modelling was used to subgroup the six fundamental copy number features and non-negative matrix factorization was used to generate the signatures and cluster the samples.ResultsWe extracted six fundamental copy number features from 69 diagnostic and pre-diagnostic cervical samples from patients diagnosed with HGSC and generated six CN signatures. We found different distributions of features in benign samples compared to tumors and cervical samples from HGSC patients. We also observed different exposures to the six signatures in different patient groups.ConclusionsFurther understanding of the components and cell types contributing to each signature, and inclusion of more cervical samples into the approach, will hopefully identify a novel tumorigenic signature for early detection of HGSC in cervical samples.
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| 2. |
- Måsbäck, Anna
(författare)
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Malignant Melanoma in southern Sweden; Histopathology, Prognosis and Aetiology
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The purpose was to study the prognostic and aetiologic risk factors for melanoma in correlation to histopathology. Paper 1-3: Thin tumours (<0.8 mm), tumours with inflammation and median age at diagnosis were signifcantly increasing in 711 CMM patients during the period 1965-89. No difference was found in median thickness. Factors that significantly improved prognosis were; thin tumour thickness, absence of ulceration, female gender, tumour location on extremities, young age and moderate/much tumour inflammation. Correlations between different factors were found, e.g. tumour localisation predominating on the back in males and on the legs in females. LMM (Lentiginous Malignant Melanoma) was seen in combination of old age and facial tumour site. Further there was a relation between thicker tumours and deeper invasion, nodular type (NM), ulceration and older age. Tumours with inflammation were related to thinner tumours, younger age, male sex, location on non-extremities and absence of naevus cells. Paper 4: In a case-control study including 366 CMM patients, a history of melanoma in the family was significantly related to thin tumours (<0.8 mm), tumour site on the trunk and non-significantly associated to younger age at diagnosis. Further the risk for developing SSM-type was significantly increased with the tendency to freckle, raised naevi, propensity to sunburn and decreased with out-door occupation. The NM-type was associated with the presence of raised naevi on the forearm and to sunburn. Absence of naevus cells in the tumour had a significant correlation to sunburn and the presence of raised naevi. Paper 5: From families with CDKN2A-mutation 26 CMM patients were identified and matched with each 3 controls. The invasive level according to Clark was significantly lower among cases compared to controls. No significant differences were seen for tumour thickness. Compared to a population-based material (n=667), cases were significantly younger at diagnosis (median age 42 vs. 61 years) and had less regressive reaction in their tumours.
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