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2. Neratinib + fulvestrant + trastuzumab for HR-positive, HER2-negative, HER2-mutant metastatic breast cancer: outcomes and biomarker analysis from the SUMMIT trial

Author

Jhaveri, K., Eli, L.D., Wildiers, H., Hurvitz, S.A., Guerrero-Zotano, A., Unni, N., Brufsky, A., Park, H., Waisman, J., Yang, E.S., Spanggaard, I., Reid, S., Burkard, M.E., Vinayak, S., Prat, A., Arnedos, M., Bidard, F.-C., Loi, S., Crown, J., Bhave, M., Piha-Paul, S.A., Suga, J.M., Chia, S., Saura, C., Garcia-Saenz, J.Á., Gambardella, V., de Miguel, M.J., Gal-Yam, E.N., Raphael, A., Stemmer, S.M., Ma, C., Hanker, A.B., Ye, D., Goldman, J.W., Bose, R., Peterson, L., Bell, J.S.K., Frazier, A., DiPrimeo, D., Wong, A., Arteaga, C.L., and Solit, D.B.

Published
2023
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3. The Relationship between Subject Matter Knowledge and Teaching Effectiveness of Undergraduate Chemistry Peer Facilitators

Author

Boothe, J. R., Barnard, R. A., Peterson, L. J., and Coppola, B. P.

Abstract

Use of peer instruction and facilitation has surged in undergraduate education at large colleges and universities in recent years. Studies on peer instruction have been directed primarily at student learning gains and affective outcomes among the facilitators. For peer instructors, the relationship between their teaching effectiveness and their foundational content knowledge is assumed but understudied. In an effort to promote instructional coherence (i.e., instructional same-pageness) in the introductory organic chemistry program at the University of Michigan, we observed peer-led study group facilitators' involvement in their study groups (as teachers of groups of 6-12 students) and in a companion course (as learners) designed to reinforce and enhance their content knowledge. Audiovisual recordings of the facilitators in both the companion course and, for ten of them, leading their study groups, were captured over each of the two week periods covering the topics of stereochemistry and also conformational analysis. Recordings were subsequently coded for topic and correctness in presentation of subject matter. Errors made in either study group or the companion course were investigated for error resolution (corrected or uncorrected), source of error, and propagation of corrected errors. Analysis of recordings revealed that facilitators who have their own errors corrected in the companion course, or observe their peers' errors corrected in the companion course, correctly describe these concepts in study groups. On examining errors made by facilitators when they are leading study group sessions, a backwards analysis showed consistently that either the topics had not been addressed in the antecedent companion course, or the facilitator was not actively engaged with the discussion when the topics were being discussed. These findings have implications to inform not only our own implementation of peer-led study groups, but also those interested in designing subject matter companion courses for peer leaders in other instructional settings.

Published
2018
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4. HEXTE Studies of Sco X-1 Spectra: Detections of Hard X-Ray Tails Beyond 200 keV

Author

D'Amico, F., Heindl, W. A., Rothschild, R. E., Peterson, L. E., Gruber, D. E., Pelling, M., and Tomsick, J. A.

Subjects
Astrophysics
Abstract

Using the HEXTE experiment on-board the RXTE satellite, we performed a search for hard X-ray tails in Sco X-1 spectra. We found strong evidence for the presence of such a non-thermal component on several occasions. Using the PCA/RXTE we were able to track the position of the source along the Z diagram, and we observed that the presence of the hard X-ray tail is not confined to a particular region. However, we found a correlation between the power law index of the non-thermal component and the position of the source in the Z diagram, suggesting that the hard X-ray spectrum (i.e., E > 50 keV) becomes flatter as the mass accretion rate increases. We were also able to study the temporal variation of the appearance/absence of the hard X-ray component. With our derived luminosities, we were also able to test the idea that X-ray luminosities can be used to distinguish between X-ray binary systems containing neutron stars and black holes., Comment: 6 pages, 2 figures; Presented at the 33rd COSPAR Scientific Assembly (Warsaw, Poland, 2000 July); Accepted for publication in Advances in Space Research

Published
2001
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5. The Spectrum of Diffuse Cosmic Hard X-Rays Measured with HEAO-1

Author

Gruber, D. E., Matteson, J. L., Peterson, L. E., and Jung, G. V.

Subjects
Astrophysics
Abstract

The spectrum of the diffuse isotropic component of cosmic X-rays over the 13-180 keV range was determined by the UCSD/MIT Hard X-Ray and Gamma-Ray instrument (HEAO A4) on the High Energy Astronomical Observatory-1 (HEAO-1). The instrument consists of a complex of actively shielded and collimated scintillation counters, including the Low Energy Detector set from which the data reported here were obtained. These data join smoothly with the spectrum at lower energies reported by the GSFC HEAO A2 instrument and with that measured to 400 keV by the HEAO A4 Medium Energy Detectors. The HEAO data set also joins the recent results from COMPTEL on the Compton Gamma-Ray Observatory in the 1-10 MeV range, which failed to confirm the existence of an "MeV bump" in this range. Although the spectrum over the entire range 3 keV < E < 100 GeV can be fit by a simple empirical analytic expression, the origin is likely due to a number of distinct source components. The prevailing idea for the origin is that the hard X-ray spectrum is due to X-rays from various AGN components, particularly Seyfert galaxies extending to cosmological distances, and that the low energy gamma-rays may be due to emission from type 1a Supernovae, also integrated to cosmological distances. The higher energy gamma-ray spectrum defined by EGRET, also on the CGRO, may be due to unresolved gamma-ray emitting blazars. Models of production by these source components, extrapolated to the present epoch, must reproduce the observationally derived spectrum., Comment: LaTeX, 16pp, 3figs

Published
1999
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7. The X-ray Spectrum of the Plerionic System PSR B1509-58/MSH 15-52

Author

Marsden, D., Blanco, P. R., Gruber, D. E., Heindl, W. A., Pelling, M. R., Peterson, L. E., Rothschild, R. E., Rots, A. H., Jahoda, K., and Macomb, D. J.

Subjects
Astrophysics
Abstract

We present the results of observations of the PSR B1509$-$58/MSH 15$-$52 system in X-rays ($2-250$ keV) by the Rossi X-ray Timing Explorer. The spectra of the peak of the pulsed component (radio phase $0.17-0.53$) is fit by a power law of photon index $1.36\pm0.01$, with no evidence of a high energy spectral break seen up to $\sim200$ keV. For the off-pulse spectral component, the spectrum from $2-250$ keV is fit by a power law of photon index $2.215\pm0.005$. An iron emission line at 6.7 keV with an equivalent width of 129 eV improves the fit, but only at a marginal significance. Thermal bremsstrahlung and Raymond-Smith models produce much worse fits to the unpulsed data. The lack of a high energy spectral break in the pulsed emission implies an efficiency of $\geq 3%$ in the conversion of pulsar spindown energy to pulsed X-rays in the system., Comment: Accepted by ApJ Letters, 18 pages, 4 postscript figures

Published
1997
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9. A Multiphysics Thermoelastoviscoplastic Damage Internal State Variable Constitutive Model including Magnetism.

Author

Malki, M., Horstemeyer, M. F., Cho, H. E., Peterson, L. A., Dickel, D., Capolungo, L., and Baskes, M. I.

Subjects
MAGNETISM, FIRST law of thermodynamics, SECOND law of thermodynamics, DEFORMATIONS (Mechanics), MAGNETIC field effects, MAGNETOSTRICTION
Abstract

We present a macroscale constitutive model that couples magnetism with thermal, elastic, plastic, and damage effects in an Internal State Variable (ISV) theory. Previous constitutive models did not include an interdependence between the internal magnetic (magnetostriction and magnetic flux) and mechanical fields. Although constitutive models explaining the mechanisms behind mechanical deformations caused by magnetization changes have been presented in the literature, they mainly focus on nanoscale structure–property relations. A fully coupled multiphysics macroscale ISV model presented herein admits lower length scale information from the nanoscale and microscale descriptions of the multiphysics behavior, thus capturing the effects of magnetic field forces with isotropic and anisotropic magnetization terms and moments under thermomechanical deformations. For the first time, this ISV modeling framework internally coheres to the kinematic, thermodynamic, and kinetic relationships of deformation using the evolving ISV histories. For the kinematics, a multiplicative decomposition of deformation gradient is employed including a magnetization term; hence, the Jacobian represents the conservation of mass and conservation of momentum including magnetism. The first and second laws of thermodynamics are used to constrain the appropriate constitutive relations through the Clausius–Duhem inequality. The kinetic framework employs a stress–strain relationship with a flow rule that couples the thermal, mechanical, and magnetic terms. Experimental data from the literature for three different materials (iron, nickel, and cobalt) are used to compare with the model's results showing good correlations. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Neratinib plus fulvestrant plus trastuzumab for HR-positive, HER2-negative, HER2-mutant metastatic breast cancer: outcomes and biomarker analysis from the SUMMIT trial

Author

Jhaveri, K, Eli, LD, Wildiers, H, Hurvitz, SA, Guerrero-Zotano, A, Unni, N, Brufsky, A, Park, H, Waisman, J, Yang, ES, Spanggaard, I, Reid, S, Burkard, ME, Vinayak, S, Prat, A, Arnedos, M, Bidard, F-C, Loi, S, Crown, J, Bhave, M, Piha-Paul, SA, Suga, JM, Chia, S, Saura, C, Garcia-Saenz, JA, Gambardella, V, de Miguel, MJ, Gal-Yam, EN, Raphael, A, Stemmer, SM, Ma, C, Hanker, AB, Ye, D, Goldman, JW, Bose, R, Peterson, L, Bell, JSK, Frazier, A, Diprimeo, D, Wong, A, Arteaga, CL, Solit, DB, Jhaveri, K, Eli, LD, Wildiers, H, Hurvitz, SA, Guerrero-Zotano, A, Unni, N, Brufsky, A, Park, H, Waisman, J, Yang, ES, Spanggaard, I, Reid, S, Burkard, ME, Vinayak, S, Prat, A, Arnedos, M, Bidard, F-C, Loi, S, Crown, J, Bhave, M, Piha-Paul, SA, Suga, JM, Chia, S, Saura, C, Garcia-Saenz, JA, Gambardella, V, de Miguel, MJ, Gal-Yam, EN, Raphael, A, Stemmer, SM, Ma, C, Hanker, AB, Ye, D, Goldman, JW, Bose, R, Peterson, L, Bell, JSK, Frazier, A, Diprimeo, D, Wong, A, Arteaga, CL, and Solit, DB

Abstract

BACKGROUND: HER2 mutations are targetable alterations in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC). In the SUMMIT basket study, patients with HER2-mutant MBC received neratinib monotherapy, neratinib + fulvestrant, or neratinib + fulvestrant + trastuzumab (N + F + T). We report results from 71 patients with HR+, HER2-mutant MBC, including 21 (seven in each arm) from a randomized substudy of fulvestrant versus fulvestrant + trastuzumab (F + T) versus N + F + T. PATIENTS AND METHODS: Patients with HR+ HER2-negative MBC with activating HER2 mutation(s) and prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy received N + F + T (oral neratinib 240 mg/day with loperamide prophylaxis, intramuscular fulvestrant 500 mg on days 1, 15, and 29 of cycle 1 then q4w, intravenous trastuzumab 8 mg/kg then 6 mg/kg q3w) or F + T or fulvestrant alone. Those whose disease progressed on F + T or fulvestrant could cross-over to N + F + T. Efficacy endpoints included investigator-assessed objective response rate (ORR), clinical benefit rate (RECIST v1.1), duration of response, and progression-free survival (PFS). Plasma and/or formalin-fixed paraffin-embedded tissue samples were collected at baseline; plasma was collected during and at end of treatment. Extracted DNA was analyzed by next-generation sequencing. RESULTS: ORR for 57 N + F + T-treated patients was 39% [95% confidence interval (CI) 26% to 52%); median PFS was 8.3 months (95% CI 6.0-15.1 months). No responses occurred in fulvestrant- or F + T-treated patients; responses in patients crossing over to N + F + T supported the requirement for neratinib in the triplet. Responses were observed in patients with ductal and lobular histology, 1 or ≥1 HER2 mutations, and co-occurring HER3 mutations. Longitudinal circulating tumor DNA sequencing revealed acquisition of additional HER2 alterations, and mutations in genes including PIK3CA, enabling further precision targeting and possible re-respon

Published
2023

13. 1599 Rapid reduction in S. aureus in atopic dermatitis subjects following dupilumab treatment

Author

Simpson, E., primary, Schlievert, P., additional, Yoshida, T., additional, Lussier, S., additional, Boguniewicz, M., additional, Hata, T., additional, Fuxench, Z. C. Chiesa, additional, De Benedetto, A., additional, Ong, P., additional, Ko, J., additional, Calatroni, A., additional, Spergel, A. Rudman, additional, Plaut, M., additional, Quataert, S., additional, Kilgore, S., additional, Peterson, L., additional, Gill, A., additional, David, G., additional, Mosmann, T., additional, Gill, S., additional, Leung, D., additional, and Beck, L., additional

Published
2023
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18. 108P Copy loss enrichment at metastatic disease progression in hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer patients treated with endocrine therapy and CDK4/6 inhibition

Author

Davis, A.A., primary, Luo, J., additional, Zheng, T., additional, Dai, C., additional, Suresh, R., additional, Ademuyiwa, F.O., additional, Rigden, C., additional, Clifton, K., additional, Weilbaecher, K., additional, Frith, A.E., additional, Tandra, P., additional, Summa, T., additional, Thomas, S., additional, Peterson, L., additional, Wang, X., additional, Du, P., additional, Jia, S., additional, King, B.L., additional, Krishnamurthy, J., additional, and Ma, C.X., additional

Published
2022
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34. sj-docx-2-car-10.1177_19476035211060506 ��� Supplemental material for 7-Tesla MRI Evaluation of the Knee, 25 Years after Cartilage Repair Surgery: The Influence of Intralesional Osteophytes on Biochemical Quality of Cartilage

Author

Janssen, M.P.F., Peters, M.J.M., Steijvers-Peeters, E.G.M., Szomolanyi, P., Jutten, E.M.C., van Rhijn, L.W., Peterson, L., Lindahl, A., Trattnig, S., and Emans, P.J.

Subjects
FOS: Clinical medicine, FOS: Biological sciences, 110323 Surgery, 110604 Sports Medicine, FOS: Health sciences, 69999 Biological Sciences not elsewhere classified, 110314 Orthopaedics
Abstract

Supplemental material, sj-docx-2-car-10.1177_19476035211060506 for 7-Tesla MRI Evaluation of the Knee, 25 Years after Cartilage Repair Surgery: The Influence of Intralesional Osteophytes on Biochemical Quality of Cartilage by M.P.F. Janssen, M.J.M. Peters, E.G.M. Steijvers-Peeters, P. Szomolanyi, E.M.C. Jutten, L.W. van Rhijn, L. Peterson, A. Lindahl, S. Trattnig and P.J. Emans in CARTILAGE

Published
2021
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35. sj-docx-1-car-10.1177_19476035211060506 ��� Supplemental material for 7-Tesla MRI Evaluation of the Knee, 25 Years after Cartilage Repair Surgery: The Influence of Intralesional Osteophytes on Biochemical Quality of Cartilage

Author

Janssen, M.P.F., Peters, M.J.M., Steijvers-Peeters, E.G.M., Szomolanyi, P., Jutten, E.M.C., van Rhijn, L.W., Peterson, L., Lindahl, A., Trattnig, S., and Emans, P.J.

Subjects
FOS: Clinical medicine, FOS: Biological sciences, 110323 Surgery, 110604 Sports Medicine, FOS: Health sciences, 69999 Biological Sciences not elsewhere classified, 110314 Orthopaedics
Abstract

Supplemental material, sj-docx-1-car-10.1177_19476035211060506 for 7-Tesla MRI Evaluation of the Knee, 25 Years after Cartilage Repair Surgery: The Influence of Intralesional Osteophytes on Biochemical Quality of Cartilage by M.P.F. Janssen, M.J.M. Peters, E.G.M. Steijvers-Peeters, P. Szomolanyi, E.M.C. Jutten, L.W. van Rhijn, L. Peterson, A. Lindahl, S. Trattnig and P.J. Emans in CARTILAGE

Published
2021
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37. Bacis nigropictus Crotch 1876

Author

Lopes, Peterson L��saro, Gasca-��lvarez, H��ctor Jaime, and Skelley, Paul E.

Subjects
Coleoptera, Insecta, Arthropoda, Animalia, Bacis, Biodiversity, Bacis nigropictus, Erotylidae, Taxonomy
Abstract

Bacis nigropictus Crotch, 1876 (Figs. 1���29, 57���60) Bacis nigropictus Crotch 1876: 557; Fleutiaux 1886: 224; Kuhnt 1909: 48, 1911: 34; Blackwelder 1945: 463, list; Alvarenga 1994: 118, catalog. Type series: Venezuela (UMZC, not examined). Zonarius limbatus Kuhnt 1910: 249, 253, fig. 14; Kuhnt 1911: 30; Blackwelder 1945: 462, list. New synonym. Lectotype, here designated: Venezuela, M��rida: M��rida (8��35���53������N, 71��8���41������W), 104093, ���999 (ZMHB, examined). Paralectotypes: Colombia���Starke col., &male;, 21678, ���971 (ZMHB, examined); ���995 (ZMHB, examined); Kuhnt det., 4678, ���997 (ZMHB, examined). Oligocorynus limbatus (Kuhnt); Alvarenga 1994: 109, catalog. Redescription. Length: 9 mm, thorax/abdomen R=1.6. Body moderately oval, subcordiform, sides slightly curved, moderately convex. Head orange with irregular vertical black band, antennae black, clypeus black apically, orange at base, pronotum black with two orange lateral maculae, mesoventrite, mesanepisterna, mesepimera and metaventrite orange, coxae and femora dark yellow, elytra dark orange with eight black maculae, abdominal ventrites dark orange (Figs. 1���4). Head (R=0.8): ocular striae restricted to eye margin, eyes faceted, interocular distance ~2/3 of head width (Fig. 5). Stridulatory organs absent at base of head in both sexes. Antennae (R=11.6): antennomeres VIII and XI elongate (Fig. 6). Clypeus (R=0.4) sub-rectangular, apex truncate (Fig. 5). Labrum (R=0.7): sub-rectangular, without apical elevation, absence of membranous cover at proximal half (Fig. 7). Epipharynx with setae in median region and at anterior margin, median region covered with microtrichiae, tormae with anterior projection reaching the basal third of labrum, posterior projection of tormae almost as long as the anterior projection (Fig. 8, arrow). Mandibles slightly asymmetrical, with three incisors, membranous lobe covered with microtrichiae on molar region, with two carinae on dorsal region, ventral cavity with internal incisor margin sinuate, left mandible with proximal incisor smaller and attached to middle incisor as a lobe (Figs. 9���12). Maxillae (R=2.7): lacinia with an apical curved hook, with long setae denser distally, palpomere I elongate, palpomeres II���III as wide as long, palpomere IV wide, galea (R=1.9) subfalciform, with moderately long setae denser distally (Figs. 13���14). Hypopharynx with two basal arms extending to posterior region of mentum (Fig. 15, arrow). Labium (R=1.5): ligula long (~3/4 width of the mentum), fused at middle, with a basal sclerite extending through almost the entire ligula, outer angles rounded, basal palpomere with moderately curved base, inner angle of distal margin slightly narrow, mentum with medial region without definite shape (Fig. 16). Thorax: pronotum (R=0.4) glossy, lateral region of posterior margin with a depression, surface of depression punctate, prosternum with few short setae, procoxal lines absent. Scutellar shield (R=0.7) semiovoid. Metaventrite (R=0.4): mesocoxal lines conspicuous. Legs: metathoracic legs with femora as wide as the prothoracic legs. Elytra (R=2.4): surface with fine punctures (��~ 0.05 mm), with elytral striae moderately conspicuous, geminate; interstriae with punctures moderately conspicuous. Metathoracic wings (R=2.3): with two axillary veins, veins AA 3+4 reaching CuA 3+4, veins MP 3+4 reaching MP 1+2, vein cua1-mp4 complete, vein r4 complete (Fig. 17). Abdomen: surface with few short setae. Male genital segments and genitalia: tergite VIII (R=0.6) subtriangular, uniformly sclerotized, base curved, setae denser distally (Fig. 18); sternite VIII (R=0.3) transverse, distal margin emarginate, setae denser distally (Fig. 19); tergite X (R=0.8) U-shaped; lateral shafts slightly curved, apex truncate, setae denser distally (Fig. 20); laterotergite IX (R=1.4) elongate, asymmetrical, lateral lobes sub-triangular; sternite IX setae denser distally (Fig. 21). Aedeagus: tegmen elongate at middle, dorsal longitudinal line sclerotized, tegmen arm long, with two sclerotized lines, lateral lobes width ~1/8 of tegmen length, setae denser distally, lateral region of median lobe narrow, internal sac short (Figs. 22���24); head of flagellum subtriangular (Fig. 25, MAAEIS). Female genital segments and genitalia: tergite VIII (R=0.5) transverse, setae denser distally (Fig. 26); sternite VIII (R=0.6) transverse, setae denser distally, median strut approximately three times longer than base (Fig. 27); tergite IX and sternite IX indistinct, membranous, surface with microtrichiae uniformly distributed. Ovipositor: proctiger lobe long (Figs. 28���29, arrow), covering the vulval lobe, subvulval lobe as wide as the basal segments of the gonocoxites, gonocoxites ~1/2 of ovipositor length with narrowed and rounded apex, gonostyli setae moderately long (Figs. 28���29). Spermatheca ellipsoidal. Intraspecific variation. Integument color from light-orange to light-brown, with bands, legs and sternites dark brown; inner spots of elytra can be fused in pairs. Diagnosis. Bacis nigropictus can be recognized among other species of Bacis by its dorsal coloration, with eight black elytral spots and pronotum orange with black longitudinal medial band, and clypeus truncate. Etymology. The genus name is derived from the Greek bacis, ���soothsayer���; the specific epithet is derived from the Latin nigro, ���black��� and pictus, ���painted, colored���, referring to the elytral and pronotal coloration. Material examined. Venezuela���ex-Coll. C. Felsche, donation 1907, 2 ex.: ���846, 845 (SMTD); ���843 (SMTD); Brazil��� &male;, Mus antiqu., ���844 (SMTD). Geographical distribution. Colombia, Venezuela (M��rida), Brazil. Remarks. Although the type series of B. nigropictus has not been examined, Crotch���s original description indicates that B. nigropictus and Oligocorynus limbatus are the same species. By comparing specimens of Oligocorynus to specimens of B. nigropictus, it is evident that the latter have an increased and more gradual curvature of the elytral sides (��� breviter ovatus ���, as described by Crotch [1876]), a trait typical of the genus Bacis, not of Oligocorynus. In any case, the diagnosis presented above places this species among those currently included in Bacis. The Venezuelan syntype of Zonarius limbatus is here chosen as the lectotype, because it came from the same type locality as Bacis nigropictus (see Crotch 1876). The Colombian syntypes of Z. limbatus are designated as paralectotypes (Figs. 57���60)., Published as part of Lopes, Peterson L��saro, Gasca-��lvarez, H��ctor Jaime & Skelley, Paul E., 2020, Redescriptions, new synonymy, new combination and new records of Bacis Dejean, 1836 and Oligocorynus Dejean, 1876 (Coleoptera: Erotylidae: Erotylinae) for Colombia, pp. 349-362 in Zootaxa 4809 (2) on pages 350-353, DOI: 10.11646/zootaxa.4809.2.6, http://zenodo.org/record/3934208, {"references":["Crotch, G. R. (1876) A revision of the coleopterous family Erotylidae. Cistula Entomologica, 1, 377 - 572.","Fleutiaux, E. (1886) Supplement au catalogue des Coleopteres de M. M. Gemminger et de Harold (Languriides et Erotylides). Annales de la Societe Entomologique de Belgique, 30, 216 - 224.","Kuhnt, P. (1909) Coleoptera, fam. Erotylidae, subfam. Erotylinae. In: Wytsman, P. (Ed.), Genera Insectorum. Fasc. 88. V. Verteneuil & L. Desmet, Brussels, pp. 1 - 139, 4 pls.","Kuhnt, P. (1911) Family Erotylidae. In: Junk, W. (Ed.), Coleopterorum catalogus, Pars 34 (15), pp. 1 - 103.","Blackwelder, R. E. (1945) Checklist of the coleopterous insects of Mexico, Central America, the West Indies, and South America. Bulletin of the United States National Museum, 185 (3), 343 - 550. https: // doi. org / 10.5479 / si. 03629236.185.3","Alvarenga, M. (1994) Catalogo dos Erotylidae (Coleoptera) Neotropicais. Revista Brasileira de Zoologia, 11 (1), 1 - 175. https: // doi. org / 10.1590 / S 0101 - 81751994000100001","Kuhnt, P. (1910) Neue Erotylidae (Col.). Mitteilungen aus dem Museum fur Naturkunde in Berlin: Deutsche Entomologische Zeitschrift, 28, 219 - 270."]}

Published
2020
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38. Oligocorynus flavomaculatus Lopes & Gasca-��lvarez & Skelley 2020, new combination

Author

Lopes, Peterson L��saro, Gasca-��lvarez, H��ctor Jaime, and Skelley, Paul E.

Subjects
Coleoptera, Insecta, Oligocorynus, Arthropoda, Animalia, Biodiversity, Erotylidae, Taxonomy, Oligocorynus flavomaculatus
Abstract

Oligocorynus flavomaculatus (Mader, 1943), new combination (Figs. 30���56) Phricobacis flavomaculatus Mader 1943: 114; Mader 1951: 203, key; Alvarenga 1994: 119, catalog. Holotype: Peru, Chanchamayo (NHMW, not examined). Redescription. Length 7 mm, thorax/abdomen R=1.4. Body moderately oval, sides subparallel, moderately convex. Head dark orange, antennae with antennomere I orange and antennomeres II to XI black, clypeus dark orange, pronotum orange, mesoventrite, mesanepisterna, mesepimera and metaventrite dark orange, coxae and femora dark orange, tibiae and tarsi black, elytra black with three orange maculae, epipleura black, ventrites dark orange (Figs. 30���33). Head (R=0.7): ocular striae absent, eyes finely faceted, interocular distance ~5/8 of head width, sub-ocular pore evident, post-mandibular lobes conspicuous with a setal tuft (Fig. 34). Stridulatory organs at base of head absent in both sexes. Antennae (R=12.1): club with three flattened antennomeres, antennomere VIII and XI elongate, antennomeres more pubescent towards club (Fig. 35). Clypeus (R=0.5): apex emarginate, lateral margins curved, central region elevated, surface with fine punctures (Fig. 34). Labrum (R=0.5): sub-elliptical, with semicircular anterior elevation, distal margin truncate, anterior angles rounded, absence of membranous cover at proximal half (Fig. 36). Epipharynx with setae in median region and at anterior margin, median region covered with microtrichiae, tormae with anterior projection reaching the basal quarter of labrum, posterior projection of tormae almost as long as the anterior projection (Fig. 37, arrow). Mandibles slightly asymmetrical, with three incisors, distal incisors narrower and sclerotized, membranous lobe covered with microtrichiae on molar region, one carina at dorsal region, ventral cavity with internal incisor margin curved, sinuate in left mandible, left mandible with proximal incisor smaller and attached to the middle incisor as a lobe (Figs. 38���41). Maxillae (R=3.3): lacinia with two apical curved teeth, with long setae denser distally, basal palpomere elongate, palpomeres II���III as wide as long, palpomere IV very long, securiform, galea (R=1.3) lobed, slightly projected, with moderately long setae denser distally (Figs. 42���43). Hypopharynx with two arms extending to anterior region of mentum (Fig. 44, arrow). Labium (R=1.6): ligula long (~3/4 width of mentum), fused at middle, basal sclerite absent, outer angles with moderate projection, setae denser on last palpomeres, basal palpomere with moderately curved base, palpomere III slightly securiform, asymmetrical, inner angle of distal margin slightly narrow, mentum with medial region without definite shape (Fig. 45). Thorax: pronotum (R=0.4) flattened, lateral region of posterior margin without depression, surface with strong punctures, prosternum with moderately long setae, basal margin of prosternum truncate, prosternal lines absent, procoxal lines absent. Scutellar shield (R=0.7) triangular. Metaventrite (R=0.4): mesocoxal lines absent, supracoxal lines conspicuous. Legs: surface of femora with sparse punctures, tibiae with dense setae and slightly expanded distally, metathoracic legs with femora as wide as the prothoracic legs. Elytra (R=2.2): subtriangular, base sinuate, surface with moderate punctures (��~ 0.1 mm), striae and inter-striae indistinct. Metathoracic wings (R=2.3): with one axillar vein, veins AA 3+4 reaching CuA 3+4, veins MP 3+4 reaching MP 1+2, vein cua1-mp4 complete, vein r4 incomplete, medial spot conspicuous (Fig. 46). Abdomen: surface fine and sparse, with few short setae, ventrite 1 with anterior elevation. Male genital segments and genitalia: tergite VIII (R=0.4) subtriangular, base curved, setae denser distally (Fig. 47), sternite VIII (R=0.3) transverse, distal margin emarginate, setae denser distally (Fig. 48), tergite X (R=0.7) U-shaped, apex slightly rounded, setae denser distally (Fig. 49), laterotergite IX (R=1.6) elongate, asymmetrical, lateral lobes sub trapezoidal; sternite IX setae denser distally (Fig. 50). Aedeagus: tegmen elongate at proximal third, dorsal longitudinal line sclerotized, with dorsal subapical spot, tegmen arm long, with a sclerotized ventral line, lateral lobe width ~1/8 of tegmen length, setae denser distally, distal region of medial lobe with a short and cylindrical projection, internal sac short (Fig. 51); head of flagellum falciform, elongate (Fig. 52, MAAEIS). Female genital segments and genitalia: tergite VIII (R=0.5) transverse, setae denser distally (Fig. 53), sternite VIII (R=0.6) transverse, setae dens- er distally, median strut approximately four times longer than base (Fig. 54), tergite IX and sternite IX indistinct, membranous, surface with microtrichiae uniformly distributed. Ovipositor: proctiger lobe long, covering the vulval lobe, subvulval lobe as wide as the basal segments of the gonocoxites, gonocoxites ~1/2 of ovipositor length with apex truncated and angulate at inner apex, gonostyli with dense setae (Figs. 55���56, arrow). Spermatheca oval. Intraspecific variation. The sizes of the elytral maculae are variable. The elytral base can be straight. Diagnosis. Oligocorynus flavomaculatus is distinguished from other Oligocorynus species by its dorsal coloration, having the elytral surface black with three orange spots and the pronotum orange, and clypeus emarginate. Etymology. The genus name is derived from the Greek oligo, ���few, scanty��� and coryno, ���club, mace���; the specific epithet is derived from the Latin flavus, ���yellow��� and maculatus, ���with spots���, referring to the antennae and the elytral coloration. Material examined. Colombia���Boyac��: Muzo (5��32���7������N, 74��10���40������W), ex-Coll. Alvarenga, M. Alvarenga det. [Oligocorynus ���sp.n.2���], homeotype, ���483 (MNRJ). Brasil���Acre: Tarauac�� (8��7���59������S, 70��46���0������W), ex-Coll. M. Viana, ex-Coll. J.E. Barriga Chile, P. Skelley det., &male;, #022163, #077131, ���1 (FSCA). Rond��nia: Ouro Preto do Oeste, s��tio Deus �� Amor (1��42���35������S, 62��15���0������W), M.F. Torres col. (26.iii.1985), P. Skelley det. 1995 [Zonarius near rugipunctatus], &male;, ���83 (MPEG); Fazenda Rancho Grande, 62 km SO Ariquemes (10��18���0������S, 62��37���48������W), C.W. & L.B. O���Brien col. (16.x.1993), P. Skelley det., &male;, ���2 (FSCA). Peru���P. Skelley det. 1994 [Zonarius near rugipunctatus], &female;, ���344 (HNHM). Geographical distribution. Colombia (Boyac��) (new country record), Brazil (Acre, Rond��nia), Peru (Chan- chamayo). Remarks. According to the unpublished thesis of Lopes (2009), Phricobacis flavomaculatus and other species in the genus Phricobacis are more related to some species of the genus Oligocorynus. A phylogenetic analysis of the genus Oligocorynus should include a study of these species. For now, based on Lopes (2009), we transfer P. flavomaculatus to Oligocorynus, becoming Oligocorynus flavomaculatus (Mader), new combination., Published as part of Lopes, Peterson L��saro, Gasca-��lvarez, H��ctor Jaime & Skelley, Paul E., 2020, Redescriptions, new synonymy, new combination and new records of Bacis Dejean, 1836 and Oligocorynus Dejean, 1876 (Coleoptera: Erotylidae: Erotylinae) for Colombia, pp. 349-362 in Zootaxa 4809 (2) on pages 355-360, DOI: 10.11646/zootaxa.4809.2.6, http://zenodo.org/record/3934208, {"references":["Mader, L. (1943) Zur kenntnis der amerikanische Erotyliden. Stettiner Entomologische Zeitung, 104, 109 - 116.","Mader, L. (1951) Die Erotyliden von Peru (Col.) [cont.]. Entomologische Arbeiten aus dem Museum G. Frey, 2, 197 - 225.","Alvarenga, M. (1994) Catalogo dos Erotylidae (Coleoptera) Neotropicais. Revista Brasileira de Zoologia, 11 (1), 1 - 175. https: // doi. org / 10.1590 / S 0101 - 81751994000100001","Lopes, P. L. (2009) Taxonomia e analise cladistica de Oligocorynus Chevrolat, 1836 sensu Alvarenga (1994) (Coleoptera, Erotylidae, Erotylinae, Erotylini). Doctoral Dissertation, Instituto de Biociencias, Universidade de Sao Paulo, 322 pp. [in Portuguese, https: // www. teses. usp. br / teses / disponiveis / 41 / 41133 / tde- 08072009 - 093526 / pt-br. php]"]}

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2020
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45. Oncogenic signaling pathways in the Cancer Genome Atlas

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Sanchez-Vega, F., Mina, M., Armenia, J., Chatila, W. K., Luna, A., La, K. C., Dimitriadoy, S., Liu, D. L., Kantheti, H. S., Saghafinia, S., Chakravarty, D., Daian, F., Gao, Q., Bailey, M. H., Liang, W. -W., Foltz, S. M., Shmulevich, I., Ding, L., Heins, Z., Ochoa, A., Gross, B., Gao, J., Zhang, H., Kundra, R., Kandoth, C., Bahceci, I., Dervishi, L., Doğrusöz, Uğur, Zhou, W., Shen, H., Laird, P. W., Way, G. P., Greene, C. S., Liang, H., Xiao, Y., Wang, C., Iavarone, A., Berger, A. H., Bivona, T. G., Lazar, A. J., Hammer, G. D., Giordano, T., Kwong, L. N., McArthur, G., Huang, C., Tward, A. D., Frederick, M. J., McCormick, F., Meyerson, M., Caesar-Johnson, S. J., Demchok, J. A., Felau, I., Kasapi, M., Ferguson, M. L., Hutter, C. M., Sofia, H. J., Tarnuzzer, R., Wang, Z., Yang, L., Zenklusen, J. C., Zhang, J. J., Chudamani, S., Liu, J., Lolla, L., Naresh, R., Pihl, T., Sun, Q., Wan, Y., Wu, Y., Cho, J., DeFreitas, T., Frazer, S., Gehlenborg, N., Getz, G., Heiman, D. I., Kim, J., Lawrence, M. S., Lin, P., Meier, S., Noble, M. S., Saksena, G., Voet, D., Bernard, B., Chambwe, N., Dhankani, V., Knijnenburg, T., Kramer, R., Leinonen, K., Liu, Y., Miller, M., Reynolds, S., Thorsson, V., Zhang, W., Akbani, R., Broom, B. M., Hegde, A. M., Ju, Z., Kanchi, R. S., Korkut, A., Li, J., Ling, S., Liu W., Lu, Y., Mills, G. B., Ng, K. -S., Rao, A., Ryan, M., Wang, J., Weinstein, J. N., Zhang, J., Abeshouse, A., de, Bruijn, I., Gross, B. E., Heins, Z. J., La, K., Ladanyi, M., Nissan, M. G., Phillips, S. M., Reznik, E., Sander, C., Schultz, N., Sheridan, R., Sumer, S. O., Sun, Y., Taylor, B. S., Anur, P., Peto, M., Spellman, P., Benz, C., Stuart, J. M., Wong, C. K., Yau, C., Hayes, D. N., Parker, J. S., Wilkerson, M. D., Ally, A., Balasundaram, M., Bowlby, R., Brooks, D., Carlsen, R., Chuah, E., Dhalla, N., Holt, R., Jones, S. J. M., Kasaian, K., Lee, D., Ma, Y., Marra, M. A., Mayo, M., Moore, R. A., Mungall, A. J., Mungall, K., Robertson, A. G., Sadeghi, S., Schein, J. E., Sipahimalani, P., Tam, A., Thiessen, N., Tse, K., Wong, T., Berger, A. C., Beroukhim, R., Cherniack, A. D., Cibulskis, C., Gabriel, S. B., Gao, G. F., Ha, G., Schumacher, S. E., Shih, J., Kucherlapati, M. H., Kucherlapati, R. S., Baylin, S., Cope, L., Danilova, L., Bootwalla, M. S., Lai, P. H., Maglinte, D. T., Van, Den, Berg, D. J., Weisenberger, D. J., Auman, J. T., Balu, S., Bodenheimer, T., Fan, C., Hoadley, K. A., Hoyle, A. P., Jefferys, S. R., Jones, C. D., Meng, S., Mieczkowski, P. A., Mose, L. E., Perou, A. H., Perou, C. M., Roach, J., Shi, Y., Simons, J. V., Skelly, T., Soloway, M. G., Tan, D., Veluvolu, U., Fan, H., Hinoue, T., Bellair, M., Chang, K., Covington, K., Creighton, C. J., Dinh, H., Doddapaneni, H., Donehower, L. A., Drummond, J., Gibbs, R. 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Lacombe, L., Têtu, B., Bergeron, A., McGraw, M., Staugaitis, S.M., Chabot, J., Hibshoosh, H., Sepulveda, A., Su, T., Wang, T., Potapova, O., Voronina, O., Desjardins, L., Mariani, O., Roman-Roman, S., Sastre, X., Stern, M.H., Cheng, F., Signoretti, S., Berchuck, A., Bigner, D., Lipp, E., Marks, J., McCall, S., McLendon, R., Secord, A., Sharp, A., Behera, M., Brat, D.J., Chen, A., Delman, K., Force, S., Khuri, F., Magliocca, K., Maithel, S., Olson, J.J., Owonikoko, T., Pickens, A., Ramalingam, S., Shin, D.M., Sica, G., Van Meir, E.G., Eijckenboom, W., Gillis, A., Korpershoek, E., Looijenga, L., Oosterhuis, W., Stoop, H., van Kessel, K.E., Zwarthoff, E.C., Calatozzolo, C., Cuppini, L., Cuzzubbo, S., DiMeco, F., Finocchiaro, G., Mattei, L., Perin, A., Pollo, B., Chen, C., Houck, J., Lohavanichbutr, P., Hartmann, A., Stoehr, C., Stoehr, R., Taubert, H., Wach, S., Wullich, B., Kycler, W., Murawa, D., Wiznerowicz, M., Chung, K., Edenfield, W.J., Martin, J., Baudin, E., Bubley, G., Bueno, R., 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Tamboli, P., Thompson, T., Troncoso, P., Tsao, A., Wistuba, I., Carter, C., Haydu, L., Hersey, P., Jakrot, V., Kakavand, H., Kefford, R., Lee, K., Long, G., Mann, G., Quinn, M., Saw, R., Scolyer, R., Shannon, K., Spillane, A., Stretch, J., Synott, M., Thompson, J., Wilmott, J., Al-Ahmadie, H., Chan, T.A., Ghossein, R., Gopalan, A., Levine, D.A., Reuter, V., Singer, S., Singh, B., Tien, N.V., Broudy, T., Mirsaidi, C., Nair, P., Drwiega, P., Miller, J., Smith, J., Zaren, H., Park, J.W., Hung, N.P., Kebebew, E., Linehan, W.M., Metwalli, A.R., Pacak, K., Pinto, P.A., Schiffman, M., Schmidt, L.S., Vocke, C.D., Wentzensen, N., Worrell, R., Yang, H., Moncrieff, M., Goparaju, C., Melamed, J., Pass, H., Botnariuc, N., Caraman, I., Cernat, M., Chemencedji, I., Clipca, A., Doruc, S., Gorincioi, G., Mura, S., Pirtac, M., Stancul, I., Tcaciuc, D., Albert, M., Alexopoulou, I., Arnaout, A., Bartlett, J., Engel, J., Gilbert, S., Parfitt, J., Sekhon, H., Thomas, G., Rassl, D.M., Rintoul, R.C., Bifulco, 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Fassnacht, M., Asa, S.L., Schadendorf, D., Couce, M., Graefen, M., Huland, H., Sauter, G., Schlomm, T., Simon, R., Tennstedt, P., Olabode, O., Nelson, M., Bathe, O., Carroll, P.R., Chan, J.M., Disaia, P., Glenn, P., Kelley, R.K., Landen, C.N., Phillips, J., Prados, M., Simko, J., Smith-McCune, K., VandenBerg, S., Roggin, K., Fehrenbach, A., Kendler, A., Sifri, S., Steele, R., Jimeno, A., Carey, F., Forgie, I., Mannelli, M., Carney, M., Hernandez, B., Campos, B., Herold-Mende, C., Jungk, C., Unterberg, A., von Deimling, A., Bossler, A., Galbraith, J., Jacobus, L., Knudson, M., Knutson, T., Ma, D., Milhem, M., Sigmund, R., Godwin, A.K., Madan, R., Rosenthal, H.G., Adebamowo, C., Adebamowo, S.N., Boussioutas, A., Beer, D., Giordano, T., Mes-Masson, A.M., Saad, F., Bocklage, T., Landrum, L., Mannel, R., Moore, K., Moxley, K., Postier, R., Walker, J., Zuna, R., Feldman, M., Valdivieso, F., Dhir, R., Luketich, J., Pinero, EMM, Quintero-Aguilo, M., Carlotti, C.G., Dos Santos, J.S., Kemp, R., 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Berger A.H., Bivona T.G., Lazar A.J., Hammer G.D., Giordano T., Kwong L.N., McArthur G., Huang C., Tward A.D., Frederick M.J., McCormick F., Meyerson M., Caesar-Johnson S.J., Demchok J.A., Felau I., Kasapi M., Ferguson M.L., Hutter C.M., Sofia H.J., Tarnuzzer R., Wang Z., Yang L., Zenklusen J.C., Zhang J.J., Chudamani S., Liu J., Lolla L., Naresh R., Pihl T., Sun Q., Wan Y., Wu Y., Cho J., DeFreitas T., Frazer S., Gehlenborg N., Getz G., Heiman D.I., Kim J., Lawrence M.S., Lin P., Meier S., Noble M.S., Saksena G., Voet D., Bernard B., Chambwe N., Dhankani V., Knijnenburg T., Kramer R., Leinonen K., Liu Y., Miller M., Reynolds S., Thorsson V., Zhang W., Akbani R., Broom B.M., Hegde A.M., Ju Z., Kanchi R.S., Korkut A., Li J., Ling S., Liu W., Lu Y., Mills G.B., Ng K.-S., Rao A., Ryan M., Wang J., Weinstein J.N., Zhang J., Abeshouse A., de Bruijn I., Gross B.E., Heins Z.J., La K., Ladanyi M., Nissan M.G., Phillips S.M., Reznik E., Sander C., Schultz N., Sheridan R., Sumer S.O., Sun Y., Taylor B.S., Anur P., Peto M., Spellman P., Benz C., Stuart J.M., Wong C.K., Yau C., Hayes D.N., Parker J.S., Wilkerson M.D., Ally A., Balasundaram M., Bowlby R., Brooks D., Carlsen R., Chuah E., Dhalla N., Holt R., Jones S.J.M., Kasaian K., Lee D., Ma Y., Marra M.A., Mayo M., Moore R.A., Mungall A.J., Mungall K., Robertson A.G., Sadeghi S., Schein J.E., Sipahimalani P., Tam A., Thiessen N., Tse K., Wong T., Berger A.C., Beroukhim R., Cherniack A.D., Cibulskis C., Gabriel S.B., Gao G.F., Ha G., Schumacher S.E., Shih J., Kucherlapati M.H., Kucherlapati R.S., Baylin S., Cope L., Danilova L., Bootwalla M.S., Lai P.H., Maglinte D.T., Van Den Berg D.J., Weisenberger D.J., Auman J.T., Balu S., Bodenheimer T., Fan C., Hoadley K.A., Hoyle A.P., Jefferys S.R., Jones C.D., Meng S., Mieczkowski P.A., Mose L.E., Perou A.H., Perou C.M., Roach J., Shi Y., Simons J.V., Skelly T., Soloway M.G., Tan D., Veluvolu U., Fan H., Hinoue T., Bellair M., Chang K., Covington K., Creighton C.J., Dinh H., Doddapaneni H., Donehower L.A., Drummond J., Gibbs R.A., Glenn R., Hale W., Han Y., Hu J., Korchina V., Lee S., Lewis L., Li W., Liu X., Morgan M., Morton D., Muzny D., Santibanez J., Sheth M., Shinbrot E., Wang L., Wang M., Wheeler D.A., Xi L., Zhao F., Hess J., Appelbaum E.L., Bailey M., Cordes M.G., Fronick C.C., Fulton L.A., Fulton R.S., Mardis E.R., McLellan M.D., Miller C.A., Schmidt H.K., Wilson R.K., Crain D., Curley E., Gardner J., Lau K., Mallery D., Morris S., Paulauskis J., Penny R., Shelton C., Shelton T., Sherman M., Thompson E., Yena P., Bowen J., Gastier-Foster J.M., Gerken M., Leraas K.M., Lichtenberg T.M., Ramirez N.C., Wise L., Zmuda E., Corcoran N., Costello T., Hovens C., Carvalho A.L., de Carvalho A.C., Fregnani J.H., Longatto-Filho A., Reis R.M., Scapulatempo-Neto C., Silveira H.C.S., Vidal D.O., Burnette A., Eschbacher J., Hermes B., Noss A., Singh R., Anderson M.L., Castro P.D., Ittmann M., Huntsman D., Kohl B., Le X., Thorp R., Andry C., Duffy E.R., Lyadov V., Paklina O., Setdikova G., Shabunin A., Tavobilov M., McPherson C., Warnick R., Berkowitz R., Cramer D., Feltmate C., Horowitz N., Kibel A., Muto M., Raut C.P., Malykh A., Barnholtz-Sloan J.S., Barrett W., Devine K., Fulop J., Ostrom Q.T., Shimmel K., Wolinsky Y., Sloan A.E., De Rose A., Giuliante F., Goodman M., Karlan B.Y., Hagedorn C.H., Eckman J., Harr J., Myers J., Tucker K., Zach L.A., Deyarmin B., Hu H., Kvecher L., Larson C., Mural R.J., Somiari S., Vicha A., Zelinka T., Bennett J., Iacocca M., Rabeno B., Swanson P., Latour M., Lacombe L., Tetu B., Bergeron A., McGraw M., Staugaitis S.M., Chabot J., Hibshoosh H., Sepulveda A., Su T., Wang T., Potapova O., Voronina O., Desjardins L., Mariani O., Roman-Roman S., Sastre X., Stern M.-H., Cheng F., Signoretti S., Berchuck A., Bigner D., Lipp E., Marks J., McCall S., McLendon R., Secord A., Sharp A., Behera M., Brat D.J., Chen A., Delman K., Force S., Khuri F., Magliocca K., Maithel S., Olson J.J., Owonikoko T., Pickens A., Ramalingam S., Shin D.M., Sica G., Van Meir E.G., Eijckenboom W., Gillis A., Korpershoek E., Looijenga L., Oosterhuis W., Stoop H., van Kessel K.E., Zwarthoff E.C., Calatozzolo C., Cuppini L., Cuzzubbo S., DiMeco F., Finocchiaro G., Mattei L., Perin A., Pollo B., Chen C., Houck J., Lohavanichbutr P., Hartmann A., Stoehr C., Stoehr R., Taubert H., Wach S., Wullich B., Kycler W., Murawa D., Wiznerowicz M., Chung K., Edenfield W.J., Martin J., Baudin E., Bubley G., Bueno R., De Rienzo A., Richards W.G., Kalkanis S., Mikkelsen T., Noushmehr H., Scarpace L., Girard N., Aymerich M., Campo E., Gine E., Guillermo A.L., Van Bang N., Hanh P.T., Phu B.D., Tang Y., Colman H., Evason K., Dottino P.R., Martignetti J.A., Gabra H., Juhl H., Akeredolu T., Stepa S., Hoon D., Ahn K., Kang K.J., Beuschlein F., Breggia A., Birrer M., Bell D., Borad M., Bryce A.H., Castle E., Chandan V., Cheville J., Copland J.A., Farnell M., Flotte T., Giama N., Ho T., Kendrick M., Kocher J.-P., Kopp K., Moser C., Nagorney D., O'Brien D., O'Neill B.P., Patel T., Petersen G., Que F., Rivera M., Roberts L., Smallridge R., Smyrk T., Stanton M., Thompson R.H., Torbenson M., Yang J.D., Zhang L., Brimo F., Ajani J.A., Gonzalez A.M.A., Behrens C., Bondaruk J., Broaddus R., Czerniak B., Esmaeli B., Fujimoto J., Gershenwald J., Guo C., Logothetis C., Meric-Bernstam F., Moran C., Ramondetta L., Rice D., Sood A., Tamboli P., Thompson T., Troncoso P., Tsao A., Wistuba I., Carter C., Haydu L., Hersey P., Jakrot V., Kakavand H., Kefford R., Lee K., Long G., Mann G., Quinn M., Saw R., Scolyer R., Shannon K., Spillane A., Stretch J., Synott M., Thompson J., Wilmott J., Al-Ahmadie H., Chan T.A., Ghossein R., Gopalan A., Levine D.A., Reuter V., Singer S., Singh B., Tien N.V., Broudy T., Mirsaidi C., Nair P., Drwiega P., Miller J., Smith J., Zaren H., Park J.-W., Hung N.P., Kebebew E., Linehan W.M., Metwalli A.R., Pacak K., Pinto P.A., Schiffman M., Schmidt L.S., Vocke C.D., Wentzensen N., Worrell R., Yang H., Moncrieff M., Goparaju C., Melamed J., Pass H., Botnariuc N., Caraman I., Cernat M., Chemencedji I., Clipca A., Doruc S., Gorincioi G., Mura S., Pirtac M., Stancul I., Tcaciuc D., Albert M., Alexopoulou I., Arnaout A., Bartlett J., Engel J., Gilbert S., Parfitt J., Sekhon H., Thomas G., Rassl D.M., Rintoul R.C., Bifulco C., Tamakawa R., Urba W., Hayward N., Timmers H., Antenucci A., Facciolo F., Grazi G., Marino M., Merola R., de Krijger R., Gimenez-Roqueplo A.-P., Piche A., Chevalier S., McKercher G., Birsoy K., Barnett G., Brewer C., Farver C., Naska T., Pennell N.A., Raymond D., Schilero C., Smolenski K., Williams F., Morrison C., Borgia J.A., Liptay M.J., Pool M., Seder C.W., Junker K., Omberg L., Dinkin M., Manikhas G., Alvaro D., Bragazzi M.C., Cardinale V., Carpino G., Gaudio E., Chesla D., Cottingham S., Dubina M., Moiseenko F., Dhanasekaran R., Becker K.-F., Janssen K.-P., Slotta-Huspenina J., Abdel-Rahman M.H., Aziz D., Bell S., Cebulla C.M., Davis A., Duell R., Elder J.B., Hilty J., Kumar B., Lang J., Lehman N.L., Mandt R., Nguyen P., Pilarski R., Rai K., Schoenfield L., Senecal K., Wakely P., Hansen P., Lechan R., Powers J., Tischler A., Grizzle W.E., Sexton K.C., Kastl A., Henderson J., Porten S., Waldmann J., Fassnacht M., Asa S.L., Schadendorf D., Couce M., Graefen M., Huland H., Sauter G., Schlomm T., Simon R., Tennstedt P., Olabode O., Nelson M., Bathe O., Carroll P.R., Chan J.M., Disaia P., Glenn P., Kelley R.K., Landen C.N., Phillips J., Prados M., Simko J., Smith-McCune K., VandenBerg S., Roggin K., Fehrenbach A., Kendler A., Sifri S., Steele R., Jimeno A., Carey F., Forgie I., Mannelli M., Carney M., Hernandez B., Campos B., Herold-Mende C., Jungk C., Unterberg A., von Deimling A., Bossler A., Galbraith J., Jacobus L., Knudson M., Knutson T., Ma D., Milhem M., Sigmund R., Godwin A.K., Madan R., Rosenthal H.G., Adebamowo C., Adebamowo S.N., Boussioutas A., Beer D., Mes-Masson A.-M., Saad F., Bocklage T., Landrum L., Mannel R., Moore K., Moxley K., Postier R., Walker J., Zuna R., Feldman M., Valdivieso F., Dhir R., Luketich J., Pinero E.M.M., Quintero-Aguilo M., Carlotti C.G., Dos Santos J.S., Kemp R., Sankarankuty A., Tirapelli D., Catto J., Agnew K., Swisher E., Creaney J., Robinson B., Shelley C.S., Godwin E.M., Kendall S., Shipman C., Bradford C., Carey T., Haddad A., Moyer J., Peterson L., Prince M., Rozek L., Wolf G., Bowman R., Fong K.M., Yang I., Korst R., Rathmell W.K., Fantacone-Campbell J.L., Hooke J.A., Kovatich A.J., Shriver C.D., DiPersio J., Drake B., Govindan R., Heath S., Ley T., Van Tine B., Westervelt P., Rubin M.A., Lee J.I., Aredes N.D., Mariamidze A., Van Allen E.M., and Ciriello G.

Subjects
0301 basic medicine, cancer genome atlas, cancer genomics, combination therapy, pan-cancer, PanCanAtlas, precision oncology, signaling pathways, TCGA, therapeutics, whole exome sequencing, Signaling pathways, Somatic cell, Wnt Protein, Cancer Genome Atlas Research Network, Biochemistry, Medical and Health Sciences, Phosphatidylinositol 3-Kinases, Transforming Growth Factor beta, Neoplasms, Databases, Genetic, LS2_1, Cancer genomics, LS4_6, 610 Medicine & health, 11 Medical and Health Sciences, Cancer, biology, Wnt signaling pathway, cancer genomic, Precision oncology, Biological Sciences, Cell cycle, DNA methylation, Signal transduction, CICLO CELULAR, Life Sciences & Biomedicine, Genes, Neoplasm, Humans, Neoplasms/genetics, Neoplasms/pathology, Phosphatidylinositol 3-Kinases/genetics, Phosphatidylinositol 3-Kinases/metabolism, Signal Transduction/genetics, Transforming Growth Factor beta/genetics, Transforming Growth Factor beta/metabolism, Tumor Suppressor Protein p53/genetics, Tumor Suppressor Protein p53/metabolism, Wnt Proteins/genetics, Wnt Proteins/metabolism, Biotechnology, Human, Signal Transduction, signaling pathway, EXPRESSION, Biochemistry & Molecular Biology, GENES, Pan-cancer, Therapeutics, General Biochemistry, Genetics and Molecular Biology, NO, Databases, 03 medical and health sciences, Genetic, Genetics, Combination therapy, Protein kinase B, Gene, SIGNATURES, Cancer genome atlas, Science & Technology, LANDSCAPE, MUTATIONS, Biochemistry, Genetics and Molecular Biology(all), Human Genome, Whole exome sequencing, Cell Biology, Transforming growth factor beta, cancer genome atla, 06 Biological Sciences, COMPREHENSIVE MOLECULAR CHARACTERIZATION, Wnt Proteins, therapeutic, Good Health and Well Being, 030104 developmental biology, Genes, PanCanAtla, biology.protein, Cancer research, Neoplasm, Phosphatidylinositol 3-Kinase, Tumor Suppressor Protein p53, Digestive Diseases, Genetics and Molecular Biology(all), Developmental Biology
Abstract

Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFβ signaling, p53 and β-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these pathways, and 57% percent of tumors had at least one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy. An integrated analysis of genetic alterations in 10 signaling pathways in >9,000 tumors profiled by TCGA highlights significant representation of individual and co-occurring actionable alterations in these pathways, suggesting opportunities for targeted and combination therapies. Michael Seiler, Peter G. Smith, Ping Zhu, Silvia Buonamici, and Lihua Yu are employees of H3 Biomedicine, Inc. Parts of this work are the subject of a patent application: WO2017040526 titled “Splice variants associated with neomorphic sf3b1 mutants.” Shouyoung Peng, Anant A. Agrawal, James Palacino, and Teng Teng are employees of H3 Biomedicine, Inc. Andrew D. Cherniack, Ashton C. Berger, and Galen F. Gao receive research support from Bayer Pharmaceuticals. Gordon B. Mills serves on the External Scientific Review Board of Astrazeneca. Anil Sood is on the Scientific Advisory Board for Kiyatec and is a shareholder in BioPath. Jonathan S. Serody receives funding from Merck, Inc. Kyle R. Covington is an employee of Castle Biosciences, Inc. Preethi H. Gunaratne is founder, CSO, and shareholder of NextmiRNA Therapeutics. Christina Yau is a part-time employee/consultant at NantOmics. Franz X. Schaub is an employee and shareholder of SEngine Precision Medicine, Inc. Carla Grandori is an employee, founder, and shareholder of SEngine Precision Medicine, Inc. Robert N. Eisenman is a member of the Scientific Advisory Boards and shareholder of Shenogen Pharma and Kronos Bio. Daniel J. Weisenberger is a consultant for Zymo Research Corporation. Joshua M. Stuart is the founder of Five3 Genomics and shareholder of NantOmics. Marc T. Goodman receives research support from Merck, Inc. Andrew J. Gentles is a consultant for Cibermed. Charles M. Perou is an equity stock holder, consultant, and Board of Directors member of BioClassifier and GeneCentric Diagnostics and is also listed as an inventor on patent applications on the Breast PAM50 and Lung Cancer Subtyping assays. Matthew Meyerson receives research support from Bayer Pharmaceuticals; is an equity holder in, consultant for, and Scientific Advisory Board chair for OrigiMed; and is an inventor of a patent for EGFR mutation diagnosis in lung cancer, licensed to LabCorp. Eduard Porta-Pardo is an inventor of a patent for domainXplorer. Han Liang is a shareholder and scientific advisor of Precision Scientific and Eagle Nebula. Da Yang is an inventor on a pending patent application describing the use of antisense oligonucleotides against specific lncRNA sequence as diagnostic and therapeutic tools. Yonghong Xiao was an employee and shareholder of TESARO, Inc. Bin Feng is an employee and shareholder of TESARO, Inc. Carter Van Waes received research funding for the study of IAP inhibitor ASTX660 through a Cooperative Agreement between NIDCD, NIH, and Astex Pharmaceuticals. Raunaq Malhotra is an employee and shareholder of Seven Bridges, Inc. Peter W. Laird serves on the Scientific Advisory Board for AnchorDx. Joel Tepper is a consultant at EMD Serono. Kenneth Wang serves on the Advisory Board for Boston Scientific, Microtech, and Olympus. Andrea Califano is a founder, shareholder, and advisory board member of DarwinHealth, Inc. and a shareholder and advisory board member of Tempus, Inc. Toni K. Choueiri serves as needed on advisory boards for Bristol-Myers Squibb, Merck, and Roche. Lawrence Kwong receives research support from Array BioPharma. Sharon E. Plon is a member of the Scientific Advisory Board for Baylor Genetics Laboratory. Beth Y. Karlan serves on the Advisory Board of Invitae.

Published
2018
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