King Ferrante I of Aragon, leading figure of the Italian Renaissance, died in 1494. The autopsy of his mummy revealed a tumor infiltrating the small pelvis. We examined the histologic and molecular features of this ancient tumor to investigate its primary origin. Hematoxylin-eosin, Van Gieson, and Alcian Blue staining showed neoplastic cells infiltrating muscular fibers and forming pseudo-glandular lumina disseminated in fibrous stroma with scarce mucus. A strong immunoreactivity of the neoplastic cells was shown for pancytokeratins and proliferating cell nuclear antigen. Molecular fingerprints were investigated by examining K-ras, BRAF, and microsatellite instability in ancient tumor DNA. Sequencing analysis showed G-to-A transition in codon 12 of K-ras. BRAF mutations and microsatellite instability were not observed. Because the presence of K-ras codon 12 mutation could be associated with exposure to chemical carcinogens, possibly present in some food items, paleodietary reconstruction of the King Ferrante I was carried out by carbon (delta(13)C) and nitrogen (delta (15)N) stable isotopes analysis. delta (13)C and delta (15)N values found in bone collagen of the King were consistent with a massive intake of animal proteins. Overall, our data show that the tumor of Ferrante I was a mucinous adenocarcinoma with molecular fingerprints characteristic of colorectal carcinogenesis linked to K-ras pathway. Paleodietary reconstruction and historical chronicles indicate a strong consumption of meat by the King. The possible abundance of dietary carcinogens, related to meat consumption, could explain the K-ras mutation causing the colorectal tumor that killed Ferrante I more than 5 centuries ago. (C) 2011 Elsevier Inc. All rights reserved.

Gene-environment interactions in the pre-Industrial Era: the cancer of King Ferrante I of Aragon (1431-1494) / Ottini, Laura; Mario, Falchetti; Marinozzi, Silvia; Angeletti, Luciana Rita; Gino, Fornaciari. - In: HUMAN PATHOLOGY. - ISSN 0046-8177. - STAMPA. - 42:3(2011), pp. 332-339. [10.1016/j.humpath.2010.07.010]

Gene-environment interactions in the pre-Industrial Era: the cancer of King Ferrante I of Aragon (1431-1494).

OTTINI, LAURA;MARINOZZI, SILVIA;ANGELETTI, Luciana Rita;
2011

Abstract

King Ferrante I of Aragon, leading figure of the Italian Renaissance, died in 1494. The autopsy of his mummy revealed a tumor infiltrating the small pelvis. We examined the histologic and molecular features of this ancient tumor to investigate its primary origin. Hematoxylin-eosin, Van Gieson, and Alcian Blue staining showed neoplastic cells infiltrating muscular fibers and forming pseudo-glandular lumina disseminated in fibrous stroma with scarce mucus. A strong immunoreactivity of the neoplastic cells was shown for pancytokeratins and proliferating cell nuclear antigen. Molecular fingerprints were investigated by examining K-ras, BRAF, and microsatellite instability in ancient tumor DNA. Sequencing analysis showed G-to-A transition in codon 12 of K-ras. BRAF mutations and microsatellite instability were not observed. Because the presence of K-ras codon 12 mutation could be associated with exposure to chemical carcinogens, possibly present in some food items, paleodietary reconstruction of the King Ferrante I was carried out by carbon (delta(13)C) and nitrogen (delta (15)N) stable isotopes analysis. delta (13)C and delta (15)N values found in bone collagen of the King were consistent with a massive intake of animal proteins. Overall, our data show that the tumor of Ferrante I was a mucinous adenocarcinoma with molecular fingerprints characteristic of colorectal carcinogenesis linked to K-ras pathway. Paleodietary reconstruction and historical chronicles indicate a strong consumption of meat by the King. The possible abundance of dietary carcinogens, related to meat consumption, could explain the K-ras mutation causing the colorectal tumor that killed Ferrante I more than 5 centuries ago. (C) 2011 Elsevier Inc. All rights reserved.
ferrante i of aragon; paleonutrion; paleopathology; ancient dna; histology
01 Pubblicazione su rivista::01a Articolo in rivista
Gene-environment interactions in the pre-Industrial Era: the cancer of King Ferrante I of Aragon (1431-1494) / Ottini, Laura; Mario, Falchetti; Marinozzi, Silvia; Angeletti, Luciana Rita; Gino, Fornaciari. - In: HUMAN PATHOLOGY. - ISSN 0046-8177. - STAMPA. - 42:3(2011), pp. 332-339. [10.1016/j.humpath.2010.07.010]
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/376575
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 17
  • ???jsp.display-item.citation.isi??? 14
social impact