Dataset Information

A transcriptional switch controls sex determination in Plasmodium falciparum – whole cell proteomics

ABSTRACT: We aim to characterize the function of P. falciparum Md1 protein in sex determination.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Plasmodium Falciparum

SUBMITTER: Functional Proteomics Platform FPP

LAB HEAD: Arthur Talman

PROVIDER: PXD035547 | Pride | 2022-10-04

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	OOM_1438800_mut.fasta	Fasta
	OOM_220621_HF2_ST_pKO_125_1_100.raw	Raw
	OOM_220621_HF2_ST_pKO_175_1_100.raw	Raw
	OOM_220621_HF_ST_NF_100_05_100.raw	Raw
	OOM_220621_HF_ST_NF_125_05_100.raw	Raw

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Project description:Metastatic disease remains one of the most urgent clinical challenges accounting for over 90% of cancer-related deaths. Yet, the identification of novel therapeutic targets to fight or prevent metastatic disease has been hampered by the limited availability of clinically relevant mouse models of metastasis formation. To address this caveat, we developed a novel preclinical mouse model of spontaneous metastatic breast cancer that recapitulates the key biological events of the metastatic cascade and mimics the clinical course of metastatic disease in humans. Exploiting the conditional K14cre;CdhF/F;Trp53F/F mouse model of de novo mammary tumor formation, we orthotopically transplanted K14cre;CdhF/F;Trp53F/F derived mouse invasive lobular carcinoma (mILC) fragments into mammary glands of wild-type syngeneic hosts. Once recipient mammary tumors were established, we mimicked the clinical setting and performed a mastectomy. Following surgery, recipient mice eventually succumbed to wide-spread clinically overt metastatic disease in lymph nodes, lungs and gastrointestinal tract. Using aCGH analyses, we explored the relationship between the genomic profiles of mammary donor tumors and paired recipient outgrowths and observed a strong correlation, indicating that the genomic profile of the parental K14cre;CdhF/F;Trp53F/F mILC is highly conserved in recipient mammary tumors. To investigate the genomic relationship between recipient mammary tumors and their metastases, we examined the correlation structure of genomic profiles derived from paired sets of primary tumors and metastases. Genomic profiles of clonally-related recipient mammary tumors were highly conserved in local and distant metastases, indicating that few genomic alterations occur during transition from a primary tumor to a distant site. To more thoroughly examine potential site-specific genomic alterations, we constructed so-called ‘delta-profiles’ by calculating the difference between the genomic profile of a recipient mammary tumor and its paired lymph node- and lung metastasis. Site-specific recurrent alterations were not observed in lymph node nor lung metastases. Taken together, these data show that genomic profiles of metastases are highly similar to those of parental recipient tumors and that, if changes occurred, they did not recur in different independent samples. We performed aCGH analyses on DNA isolated from K14cre;Cdh-/-;Trp53-/- derived donor mILCs (n=3) and their recipient mammary tumor outgrowths (n=10). Furthermore, we also analyzed genomic profiles derived from lung (n=10), tumor-draining (n=7) and distant lymph node metastases (n=5) isolated from the same recipient mice. DNA from each of these samples was hybridized against related donor splenic DNA.

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A transcriptional switch controls sex determination in Plasmodium falciparum – whole cell proteomics

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